Sample records for acid clearance time

  1. Not All Children with Cystic Fibrosis Have Abnormal Esophageal Neutralization during Chemical Clearance of Acid Reflux.

    PubMed

    Woodley, Frederick W; Moore-Clingenpeel, Melissa; Machado, Rodrigo Strehl; Nemastil, Christopher J; Jadcherla, Sudarshan R; Hayes, Don; Kopp, Benjamin T; Kaul, Ajay; Di Lorenzo, Carlo; Mousa, Hayat

    2017-09-01

    Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range. Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis. Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis ( p =0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis. Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

  2. Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett’s Esophagus Than in Healthy Controls

    PubMed Central

    Lottrup, Christian; Krarup, Anne L; Gregersen, Hans; Ejstrud, Per; Drewes, Asbjørn M

    2016-01-01

    Background/Aims Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett’s esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett’s esophagus to that in healthy controls. Methods A total of 26 patients with histology-confirmed Barrett’s esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. Results Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pH-measurement and acid clearance test were not correlated (all P > 0.3). Conclusions More frequent swallowing and thus faster acid clearance in Barrett’s esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes. PMID:27557545

  3. Alterations in myocardial free fatty acid clearance precede mechanical abnormalities in canine tachycardia-induced heart failure.

    PubMed

    Freeman, G L; Colston, J T; Miller, D D

    1994-01-01

    The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([123I]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment. The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [123I]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition.

  4. Time-of-Flight Tip-Clearance Measurements

    NASA Technical Reports Server (NTRS)

    Dhadwal, H. S.; Kurkov, A. P.; Janetzke, D. C.

    1999-01-01

    In this paper a time-of-flight probe system incorporating the two integrated fiber optic probes which are tilted equally relative to the probe holder centerline, is applied for the first time to measure the tip clearance of an advanced fan prototype. Tip clearance is largely independent of the signal amplitude and it relies on timing measurement. This work exposes optical effects associated with the fan blade stagger angle that were absent during the original spin-rig experiment on the zero stagger rotor. Individual blade tip clearances were measured with accuracy of +/- 127-mm (+/- 0.005-in). Probe features are discussed and improvements to the design are suggested.

  5. Relationship between rhinosinusitis symptoms and mucociliary clearance time.

    PubMed

    Boatsman, Justin E; Calhoun, Karen H; Ryan, Matthew W

    2006-03-01

    To determine the correlation between rhinosinusitis symptoms as assessed by the Sino-Nasal Outcomes Test-20 (SNOT-20) and mucociliary clearance as assessed by the saccharin method. This was a cross-sectional study of 50 adult volunteers. Subjects completed the SNOT-20, and mucociliary clearance was determined with the saccharine method. Correlation coefficients (Spearman's Rho) were calculated for the global SNOT-20 score. The SNOT-20 scores varied from 20 to 54 (mean 30.28) with a possible range of 20 to 100. Clearance times varied from 418 to 2865 seconds (mean 999). There was no significant correlation between global SNOT-20 score and clearance time (r = 0.196). There is no significant correlation between rhinosinusitis symptoms as assessed by SNOT-20 scores and mucociliary clearance. Mucociliary clearance is important for the health of the sinonasal cavities, but clearance time does not appear to be associated with symptom severity in the population studied. A-1b.

  6. Lung-clearance mechanisms following inhalation of acid sulfates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wolff, R.K.; Muggenburg, B.A.; Silbaugh, S.A.

    1982-08-01

    These studies have indicated that acute exposures (1-6 hrs) to sulfuric acid at levels of 0.5 to 1.0 mg/m/sup 3/ can produce impairments in mucous clearance. The impairments can last for up to a week following a 1 hr exposure. These effects and studies by others suggest that high sulfate levels in polluted conditions may be one factor in observed increases of hospital visits for respiratory problems. Long term exposures to elevated levels of sulfates resulting in decreases of clearance could also be an initiating factor in producing chronic obstructive pulmonary disease (COPD). These studies have also shown that itmore » is the larger size fraction (0.6 to 1.0 ..mu..m) of sulfuric acid mist in the urban aerosol which is predominantly responsible for at least the acute effects.« less

  7. The effect of pregnancy on renal clearance of boron in rats given boric acid orally.

    PubMed

    Vaziri, N D; Oveisi, F; Culver, B D; Pahl, M V; Andersen, M E; Strong, P L; Murray, F J

    2001-04-01

    Boric acid (H(3)BO(3)) has been shown to cause developmental abnormalities in the offspring of pregnant rats. Comparative data on the renal clearance of boron (B) in rats and humans, both pregnant and nonpregnant, exposed to boric acid (BA) would reduce uncertainty in interspecies extrapolation from rats to humans. The purpose of this study was to evaluate the effect of pregnancy on the plasma half-life and renal clearance of boron in Sprague-Dawley rats given a single oral dose of boric acid. For the half-life study, nonpregnant and pregnant (gestation day 16) rats were given a single dose of 30 mg/kg of boric acid by gavage, and plasma samples were collected at 2-3 h intervals. The plasma half-life of boron was determined to be 2.9 +/- 0.2 and 3.2 +/- 0.3 h in nonpregnant and pregnant rats, respectively. In the clearance study, nonpregnant and pregnant (GD 16) rats were given a single gavage dose of 0.3, 3, or 30 mg/kg of boric acid. Boron clearance was slightly higher in pregnant rats (3.3 +/- 0.6, 3.2 +/- 0.5, and 3.4 +/- 0.5 ml/min/kg, respectively) compared to nonpregnant rats (3.1 +/- 0.8, 3.0 +/- 0.6, and 3.2 +/- 0.5 ml/min/kg, respectively), but the difference was not statistically significant and not dose-related. Boron clearance was less than creatinine clearance, suggesting tubular reabsorption in both groups. In conclusion, pregnancy did not appear to significantly alter the renal clearance or the plasma half-life of boron in Sprague-Dawley rats under the conditions of this study.

  8. Estimation of Glomerular Filtration Rate from Plasma Clearance of 51-Chromium Edetic Acid

    PubMed Central

    Chantler, C.; Barratt, T. M.

    1972-01-01

    The glomerular filtration rate was estimated by a single compartment analysis of the rate of fall of plasma concentration of 51-chromium edetic acid after a single intravenous injection. This slope clearance consistently overestimated the simultaneously determined standard urinary clearance, but could be used to predict the latter with an accuracy of ±9% (95% confidence limits). The coefficient of variation of replicate estimates of the slope clearance in the same individual was 3·9%; thus two estimates of glomerular filtration rate by this technique which differ by 11% have a 95% probability of reflecting a genuine difference. The method requires an intravenous injection and blood samples at 2 and 4 hours; urine samples are not required. It is simple, safe, and precise, and is applicable to children. PMID:4625784

  9. Effect of neurotrauma on hepatic drug clearance.

    PubMed

    Boucher, B A; Kuhl, D A; Fabian, T C; Robertson, J T

    1991-11-01

    Lorazepam, antipyrine, and indocyanine green were administered to 10 patients with severe head injuries as marker substrates of hepatic glucuronidation, oxidation, and hepatic blood flow, respectively. Pharmacokinetic parameter estimates were determined at baseline (20 to 80 hours after injury) and up to three additional times thereafter (study days 4, 7, and 14). Antipyrine clearance was increased significantly from baseline (0.50 +/- 0.31 ml/min/kg) on study days 4, 7, and 14 (p less than 0.0001). Increases in antipyrine clearance from baseline to the last study day were observed in all study patients ranging from 14% to 207%. A significant increase was also observed in lorazepam clearance on study day 14 relative to baseline (1.39 +/- 0.56 ml/min/kg) (p less than 0.005). Increases in lorazepam clearance occurred in seven of nine patients over time ranging from 9% to 130%. The unbound fraction of lorazepam did not change significantly over the study period. Likewise, no significant change was observed in the clearance of indocyanine green over time. Antipyrine clearance and alpha 1-acid glycoprotein (r = 0.41), and lorazepam clearance and C-reactive protein (r = -0.38) were significantly correlated (p less than 0.05). Similarly, antipyrine and lorazepam clearances were significantly correlated with injury severity based on the Acute Physiologic and Chronic Health Evaluation (APACHE II) score (r = -0.43 and r = -0.37, respectively). These findings suggest that hepatic oxidative and conjugative metabolism increase significantly over time in patients after acute head injury. An awareness of the potential for pharmacokinetic alterations in similarly metabolized drugs used for patients with severe head injuries is recommended.

  10. Hypoalbuminemia Is Significantly Associated with Increased Clearance Time of High Dose Methotrexate in Patients Being Treated for Lymphoma or Leukemia

    PubMed Central

    Reiss, Samantha; Buie, Larry; Adel, Nelly; Goldman, Debra A.; Devlin, Sean M.; Douer, Dan

    2017-01-01

    As a weak acid, methotrexate (MTX) is bound to serum albumin and has variable protein binding. The purpose of this study was to assess serum albumin’s relationship with MTX pharmacokinetics by comparing MTX clearance and toxicities between patients with normal serum albumin to those with hypoalbuminemia. This single-center retrospective study included adult patients with leukemia or lymphoma who received their first MTX at a dose ≥ 1 gram/m2. Hypoalbuminemia was defined as serum albumin ≤ 3.4 g/dL. MTX clearance was defined as the first documented time the MTX level ≤ 0.05 micromolar. Fisher’s Exact tests and Wilcoxon Rank Sum tests were used to examine differences in toxicities and Cox proportional hazards regression was used to assess relationship with time to clearance. Of 523 patients identified, 167 patients were evaluable. One hundred thirty five patients had normal serum albumin and 32 had hypoalbuminemia. Hypoalbuminemia was associated with a higher proportion of patients experiencing edema, ascites or pleural effusions (34% vs. 12% p=0.006) and the concomitant use of nephrotoxic agents (41% vs. 20% p=0.021). Hypoalbuminemia was associated with a significantly longer time to methotrexate clearance (median: 96 hours vs 72 hour p=0.004). In addition, patients with hypoalbuminemia had a higher proportion of hyperbilirubinemia and significantly longer hospitalization (median 14 days vs. 5 days p<0.001). In conclusion, hypoalbuminemia was associated with increased time to MTX clearance and increase length of hospitalization. High dose MTX is safe to administer in patients with low albumin levels, with appropriate leucovorin rescue and good supportive care. PMID:27542957

  11. Cellular uptake mechanism and clearance kinetics of fluorescence-labeled glycyrrhetinic acid and glycyrrhetinic acid-modified liposome in hepatocellular carcinoma cells.

    PubMed

    Sun, Yuqi; Lu, Jinghua; Yan, Dongxue; Shen, Liping; Hu, Haiyang; Chen, Dawei

    2017-07-01

    Glycyrrhetinic acid (GA) is a natural pentacyclic triterpene derivative that exerts significant effects in the suppression of liver cancer. The receptors of GA on liver cells and hepatocellular carcinoma (HCC) cells have drawn broad attention. The effects of GA might depend on its transport into and out of cells. However, the question has not been previously addressed despite its obvious and fundamental importance. In this paper, GA and GA-modified liposome (GA-Lip) were labeled with fluorescein isothiocyanate (FITC) or coumarin 6 (Cou6) using chemical or pharmaceutical techniques. The transport courses of FITC-GA and GA-Cou6-Lip were studied in HepG2 cells in vitro. We found that the fluorescence labeled GA and GA-Lip uptake and clearance were time-dependent. FITC-GA uptake involved passive diffusion and active transport, and the receptors were in the cytomembrane proteins. GA-Cou6-Lip uptake was mediated by caveolae-dependent endocytosis. In addition, FITC-GA and GA-Cou6-Lip clearance of the HCC cells fitted exponential decay and second-order processes, respectively. These findings provide new insights into the anti-HCC actions of GA. Copyright © 2017. Published by Elsevier B.V.

  12. Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

    PubMed

    De Cock, Pieter A J G; Standing, Joseph F; Barker, Charlotte I S; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G; Delanghe, Joris R; Robays, Hugo; De Paepe, Peter

    2015-11-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].). Copyright © 2015, American

  13. Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans.

    PubMed

    Carpentier, André C; Frisch, Frédérique; Brassard, Pascal; Lavoie, François; Bourbonnais, Annie; Cyr, Denis; Giguère, Robert; Baillargeon, Jean-Patrice

    2007-03-01

    Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28+/-3 yr, body mass index: 27.2+/-1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin+Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P<0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P<0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P<0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

  14. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system.

    PubMed

    Ren, Huixia; Luo, Chuanming; Feng, Yanqing; Yao, Xiaoli; Shi, Zhe; Liang, Fengyin; Kang, Jing X; Wan, Jian-Bo; Pei, Zhong; Su, Huanxing

    2017-01-01

    Impairment of amyloid-β (Aβ) clearance leads to Aβ accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial Aβ clearance from the brain and resist Aβ injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular Aβ. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after Aβ injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing Aβ accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-β clearance from the brain through mediating the function of the glymphatic system. © FASEB.

  15. Physiological and histological alterations in the bronchial mucociliary clearance system of rabbits following intermittent oral or nasal inhalation of sulfuric acid mist

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schlesinger, R.B.; Naumann, B.D.; Chen, L.C.

    Rabbits were exposed to submicrometer sulfuric acid mist (H/sub 2/SO/sub 4/) for 1 h/d, 5 d/w for 4 wk, during which time mucociliary clearance was monitored by external in vivo measurements of tagged tracer aerosol retention. One group was exposed orally to 250 ..mu..g/m/sup 3/, another to the same concentration via the nose, and a third to 500 ..mu..g/m/sup 3/ also via nasal breathing. Clearance was accelerated on specific individual days during the course of the acid exposures, especially at 500 ..mu..g/m/sup 3/. In all series, clearance was significantly faster, compared to preexposure controls, during a 2-wk follow-up period aftermore » acid exposures had ceased. At the end of this period, the rabbits were sacrificed, and histological sections were obtained from the tracheobronchial tree. Significantly increased epithelial thickness of small conducting airways, compared to sham exposure controls, occurred in rabbits exposed orally at 250 ..mu..g/m/sup 3/ or nasally at 500 ..mu.., and additionally the lumen of the smallest airways of the former group was narrower than control. The number of airways containing epithelial secretory cells was also significantly greater in these acid exposure groups compared to sham controls. The only change in the rabbits exposed nasally at 250 ..mu..g/m/sup 3/ was a significant increase in the number of airways with epithelial secretory cells in the smallest airway classfication. Differences in site and degree of histological response and degree of physiological change between the two groups exposed to identical acid concentrations appear to have been due to differences in exposure mode, with resultant effects on breathing pattern, aerosol size distribution, and concentration penetrating beyond the upper respiratory tract to specific lung sites.« less

  16. Higher serum levels of uric acid are associated with a reduced insulin clearance in non-diabetic individuals.

    PubMed

    Fiorentino, Teresa Vanessa; Sesti, Franz; Succurro, Elena; Pedace, Elisabetta; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Perticone, Francesco; Sesti, Giorgio

    2018-05-17

    Decreased insulin clearance has been reported to be associated with insulin resistance-related disorders and incident type 2 diabetes. The aim of this study was to evaluate whether higher levels of uric acid (UA), a known risk factor of type 2 diabetes, are associated with a reduced insulin clearance. 440 non-diabetic individuals were stratified in tertiles according to serum UA levels. Insulin clearance and skeletal muscle insulin sensitivity were assessed by euglycemic hyperinsulinemic clamp. Hepatic insulin resistance was estimated by the liver IR index. Subjects with higher levels of UA displayed an unfavorable metabolic phenotype with a worse lipid profile, increased levels of 2-h post-load glucose levels, fasting, and 2-h post-load insulin levels, hsCRP, liver IR index, and lower levels of eGFR and skeletal muscle insulin sensitivity, in comparison to individuals with lower UA levels. Moreover, subjects with higher UA concentrations exhibited decreased levels of insulin clearance even after adjustment for age, gender, BMI, eGFR, and skeletal muscle insulin sensitivity. In a multivariate regression analysis model including several confounding factors, UA concentration was an independent predictor of insulin clearance (β = - 0.145; P = 0.03). However, when liver IR index was included in the model, the independent association between UA levels and insulin clearance was not retained. Accordingly, in a mediation analysis, liver IR index was a mediator of the negative effects of UA levels on insulin clearance (t = - 2.55, P = 0.01). Higher serum levels of UA may affect insulin clearance by impairing hepatic insulin sensitivity.

  17. A Randomized Controlled Comparison of Esophageal Clearance Times of Oral Budesonide Preparations.

    PubMed

    Hefner, Jody N; Howard, Robin S; Massey, Robert; Valencia, Miland; Stocker, Derek J; Philla, Katherine Q; Goldman, Matthew D; Nylund, Cade M; Min, Steve B

    2016-06-01

    Topical steroids prepared as oral viscous slurries have become common in the treatment of eosinophilic esophagitis. Esophageal mucosal contact time correlates with clinical and histologic improvement. To compare the mucosal contact time of alternative oral viscous budesonide (OVB) slurries with the conventional sucralose OVB. A blinded randomized crossover trial investigating esophageal clearance of three OVB slurry preparations was done on healthy adults. Honey and xanthan gum OVB slurries were compared with standard sucralose OVB in 24 randomly assigned subjects. Each subject ingested the sucralose OVB and either the honey or xanthan gum OVB slurries. The esophageal clearance of each slurry was evaluated as an area under the curve (AUC) using 1 millicurie of technetium-99m-sulfur colloid (Tc99) co-administered in each OVB preparation using nuclear scintigraphy. A standardized taste survey was also administered. Xanthan gum had greater mucosal contact time compared to sucralose as measured by a higher AUC at 3 min (P = 0.002), while honey showed no significant difference in esophageal clearance relative to sucralose. Taste scores were significantly higher in the honey group, while scores for xanthan gum were no different from standard sucralose. OVB slurries utilizing xanthan gum may be a superior alternative to a sucralose-based slurry due to its increased mucosal contact time and similar taste tolerance. Honey may be a suitable alternative as well, due to its similar contact time and favorable taste.

  18. Method to improve the blade tip-timing accuracy of fiber bundle sensor under varying tip clearance

    NASA Astrophysics Data System (ADS)

    Duan, Fajie; Zhang, Jilong; Jiang, Jiajia; Guo, Haotian; Ye, Dechao

    2016-01-01

    Blade vibration measurement based on the blade tip-timing method has become an industry-standard procedure. Fiber bundle sensors are widely used for tip-timing measurement. However, the variation of clearance between the sensor and the blade will bring a tip-timing error to fiber bundle sensors due to the change in signal amplitude. This article presents methods based on software and hardware to reduce the error caused by the tip clearance change. The software method utilizes both the rising and falling edges of the tip-timing signal to determine the blade arrival time, and a calibration process suitable for asymmetric tip-timing signals is presented. The hardware method uses an automatic gain control circuit to stabilize the signal amplitude. Experiments are conducted and the results prove that both methods can effectively reduce the impact of tip clearance variation on the blade tip-timing and improve the accuracy of measurements.

  19. No association between endogenous retinoic acid and human papillomavirus clearance or incident cervical lesions in Brazilian women

    PubMed Central

    Siegel, Erin M.; Salemi, Jason L.; Craft, Neal E.; Villa, Luisa L.; Ferenczy, Alex; Franco, Eduardo L.; Giuliano, Anna R.

    2010-01-01

    Background Although oncogenic human papillomavirus (HPV) infections have been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to squamous cervical lesions. The activity of HPV is tightly associated with epithelial cell differentiation; therefore regulators of differentiation, such as retinoic acid, have been considered targets for the prevention of HPV-associated squamous intraepithelial lesion (SIL) development. Purpose The purpose of this study was to determine the association between circulating retinoic acid (RA) and early events in cervical carcinogenesis, specifically type-specific HPV clearance and SIL detection. Methods Archived blood samples from 643 women participating in the Ludwig-McGill Cohort in São Paulo, Brazil were analyzed by high-pressure liquid chromatography for three RA isomers (all-trans, 13-cis, and 9-cis RA). A type-specific HPV clearance event was defined as two consecutive visits negative for that HPV type during follow-up for the 364 HPV positive women. Among the 643 women in this analysis, 78 were diagnosed with incident SIL. Results The probability of clearing an oncogenic HPV infection was not significantly different across RA isomer quartiles. There was a suggestion that increasing all-trans RA increased rate of non-oncogenic HPV clearance (p-trend=0.05). There was no association observed between serum RA levels and incident SIL. Conclusions Our results suggest that elevated circulating RA isomer levels do not increase rates of HPV clearance or reduce risk of incident SIL. The role of RA in the inhibition of HPV induced carcinogenesis, as demonstrated in vitro, lacks confirmatory evidence within epidemiologic studies among women. PMID:20606041

  20. Turbine blade tip clearance measurements using skewed dual optical beams of tip timing

    NASA Astrophysics Data System (ADS)

    Ye, De-chao; Duan, Fa-jie; Guo, Hao-tian; Li, Yangzong; Wang, Kai

    2011-12-01

    Optimization and active control of the clearance between turbine blades and case of the engine is identified, especially in aerospace community, as a key technology to increase engine efficiency, reduce fuel consumption and emissions and increase service life .However, the tip clearance varies during different operating conditions. Thus a reliable non-contact and online detection system is essential and ultimately used to close the tip clearance control loop. This paper described a fiber optical clearance measuring system applying skewed dual optical beams to detect the traverse time of passing blades. Two beams were specially designed with an outward angle of 18 degree and the beam spot diameters are less than 100μm within 0-4mm working range to achieve high signal-to-noise and high sensitivity. It could be theoretically analyzed that the measuring accuracy is not compromised by degradation of signal intensity caused by any number of environmental conditions such as light source instability, contamination and blade tip imperfection. Experimental tests were undertaken to achieve a high resolution of 10µm in the rotational speed range 2000-18000RPM and a measurement accuracy of 15μm, indicating that the system is capable of providing accurate and reliable data for active clearance control (ACC).

  1. Physiological analysis of the effects of rikkunshito on acid and non-acid gastroesophageal reflux using pH-multichannel intraluminal impedance monitoring.

    PubMed

    Kawahara, Hisayoshi; Tazuke, Yuko; Soh, Hideki; Yoneda, Akihiro; Fukuzawa, Masahiro

    2014-09-01

    To clarify the effects of rikkunshito on acid reflux, non-acid reflux, and esophageal clearance in patients with gastroesophageal reflux disease (GERD). We enrolled seven patients with vomiting and/or stridor (median 6 years; 1 month-17 years), with a percent total time of esophageal pH <4.0 (reflux index) over 4.0%. Rikkunshito (TJ-43; Tsumura Co, Tokyo, Japan) was given in three divided doses before meals. We retrospectively investigated its efficacy using pH-multichannel intraluminal impedance before and 7 (6-10) days after starting treatment. Statistical analyses were conducted using Wilcoxon signed-rank test. In the pH analyses alone, the median number of acid reflux episodes >5 min (14 versus 10, p = 0.046) and median acid-clearance time (184 versus 134 s, p = 0.03) decreased significantly, although median decrease in reflux index did not reach significance (16.0 versus 17.9%, p = 0.06). In the combined impedance and pH analyses, the median number (36 versus 36, p = 0.03) and median duration (1.9 versus 1.1%, p = 0.046) of acid reflux decreased significantly; non-acid reflux and bolus clearance time did not change. Rikkunshito effectively reduced acid reflux, but not esophageal clearance, in patients with GERD.

  2. Diverse Data Sets Can Yield Reliable Information through Mechanistic Modeling: Salicylic Acid Clearance.

    PubMed

    Raymond, G M; Bassingthwaighte, J B

    This is a practical example of a powerful research strategy: putting together data from studies covering a diversity of conditions can yield a scientifically sound grasp of the phenomenon when the individual observations failed to provide definitive understanding. The rationale is that defining a realistic, quantitative, explanatory hypothesis for the whole set of studies, brings about a "consilience" of the often competing hypotheses considered for individual data sets. An internally consistent conjecture linking multiple data sets simultaneously provides stronger evidence on the characteristics of a system than does analysis of individual data sets limited to narrow ranges of conditions. Our example examines three very different data sets on the clearance of salicylic acid from humans: a high concentration set from aspirin overdoses; a set with medium concentrations from a research study on the influences of the route of administration and of sex on the clearance kinetics, and a set on low dose aspirin for cardiovascular health. Three models were tested: (1) a first order reaction, (2) a Michaelis-Menten (M-M) approach, and (3) an enzyme kinetic model with forward and backward reactions. The reaction rates found from model 1 were distinctly different for the three data sets, having no commonality. The M-M model 2 fitted each of the three data sets but gave a reliable estimates of the Michaelis constant only for the medium level data (K m = 24±5.4 mg/L); analyzing the three data sets together with model 2 gave K m = 18±2.6 mg/L. (Estimating parameters using larger numbers of data points in an optimization increases the degrees of freedom, constraining the range of the estimates). Using the enzyme kinetic model (3) increased the number of free parameters but nevertheless improved the goodness of fit to the combined data sets, giving tighter constraints, and a lower estimated K m = 14.6±2.9 mg/L, demonstrating that fitting diverse data sets with a single model

  3. Inherited Disorders of Bilirubin Clearance

    PubMed Central

    Memon, Naureen; Weinberger, Barry I; Hegyi, Thomas; Aleksunes, Lauren M

    2016-01-01

    Inherited disorders of hyperbilirubinemia may be caused by increased bilirubin production or decreased bilirubin clearance. Reduced hepatic bilirubin clearance can be due to defective 1) unconjugated bilirubin uptake and intrahepatic storage, 2) conjugation of glucuronic acid to bilirubin (e.g. Gilbert syndrome, Crigler-Najjar syndrome, Lucey-Driscoll syndrome, breast milk jaundice), 3) bilirubin excretion into bile (Dubin-Johnson syndrome), or 4) conjugated bilirubin re-uptake (Rotor syndrome). In this review, the molecular mechanisms and clinical manifestations of these conditions are described, as well as current approaches to diagnosis and therapy. PMID:26595536

  4. Hepatic drug clearance following traumatic injury.

    PubMed

    Slaughter, R L; Hassett, J M

    1985-11-01

    Trauma is a complex disease state associated with physiologic changes that have the potential to alter hepatic drug clearance mechanisms. These responses include alterations in hepatic blood flow, reduction in hepatic microsomal activity, reduction in hepatic excretion processes, and changes in protein binding. Hepatic blood flow is influenced by sympathomimetic activity. Both animal and human studies demonstrate an initial reduction and subsequent increase in hepatic blood flow, which coincides with an observed increase and subsequent return to normal in serum catecholamine concentrations. Unfortunately, there are no human studies that address the importance these findings may have to the clearance processes of high intrinsic clearance compounds. Animal studies of trauma indicate that hepatic microsomal activity is depressed during the post-traumatic period. Reduction in the hepatic clearance of antipyrine, a model low intrinsic compound, has also been demonstrated in animal models of trauma. In addition to these effects, hepatic excretion of substances such as indocyanine green and bilirubin have been demonstrated to be impaired in both traumatized animals and humans. Finally, substantial increases in the serum concentration of the binding protein alpha 1-acid glycoprotein occur in trauma patients. This has been reported to be associated with subsequent decreases in the free fraction of lidocaine and quinidine. In addition to changing serum drug concentration/response relationships, the pharmacokinetic behavior of drugs bound to alpha 1-acid glycoprotein should also change. Preliminary observations in our laboratory in a dog model of surgically-induced trauma have shown a reduction in the total clearance of lidocaine and reduction in free lidocaine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Comparison of 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA) metabolism and kinetics in the isolated rat heart.

    PubMed

    DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J

    1988-01-01

    Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue:albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.

  6. An optical fiber bundle sensor for tip clearance and tip timing measurements in a turbine rig.

    PubMed

    García, Iker; Beloki, Josu; Zubia, Joseba; Aldabaldetreku, Gotzon; Illarramendi, María Asunción; Jiménez, Felipe

    2013-06-05

    When it comes to measuring blade-tip clearance or blade-tip timing in turbines, reflective intensity-modulated optical fiber sensors overcome several traditional limitations of capacitive, inductive or discharging probe sensors. This paper presents the signals and results corresponding to the third stage of a multistage turbine rig, obtained from a transonic wind-tunnel test. The probe is based on a trifurcated bundle of optical fibers that is mounted on the turbine casing. To eliminate the influence of light source intensity variations and blade surface reflectivity, the sensing principle is based on the quotient of the voltages obtained from the two receiving bundle legs. A discrepancy lower than 3% with respect to a commercial sensor was observed in tip clearance measurements. Regarding tip timing measurements, the travel wave spectrum was obtained, which provides the average vibration amplitude for all blades at a particular nodal diameter. With this approach, both blade-tip timing and tip clearance measurements can be carried out simultaneously. The results obtained on the test turbine rig demonstrate the suitability and reliability of the type of sensor used, and suggest the possibility of performing these measurements in real turbines under real working conditions.

  7. An Optical Fiber Bundle Sensor for Tip Clearance and Tip Timing Measurements in a Turbine Rig

    PubMed Central

    García, Iker; Beloki, Josu; Zubia, Joseba; Aldabaldetreku, Gotzon; Illarramendi, María Asunción; Jiménez, Felipe

    2013-01-01

    When it comes to measuring blade-tip clearance or blade-tip timing in turbines, reflective intensity-modulated optical fiber sensors overcome several traditional limitations of capacitive, inductive or discharging probe sensors. This paper presents the signals and results corresponding to the third stage of a multistage turbine rig, obtained from a transonic wind-tunnel test. The probe is based on a trifurcated bundle of optical fibers that is mounted on the turbine casing. To eliminate the influence of light source intensity variations and blade surface reflectivity, the sensing principle is based on the quotient of the voltages obtained from the two receiving bundle legs. A discrepancy lower than 3% with respect to a commercial sensor was observed in tip clearance measurements. Regarding tip timing measurements, the travel wave spectrum was obtained, which provides the average vibration amplitude for all blades at a particular nodal diameter. With this approach, both blade-tip timing and tip clearance measurements can be carried out simultaneously. The results obtained on the test turbine rig demonstrate the suitability and reliability of the type of sensor used, and suggest the possibility of performing these measurements in real turbines under real working conditions. PMID:23739163

  8. Improvements in Obstacle Clearance Parameters and Reaction Time Over a Series of Obstacles Revealed After Five Repeated Testing Sessions in Older Adults.

    PubMed

    Jehu, Deborah A; Lajoie, Yves; Paquet, Nicole

    2017-12-21

    The purpose of this study was to investigate obstacle clearance and reaction time parameters when crossing a series of six obstacles in older adults. A second aim was to examine the repeated exposure of this testing protocol once per week for 5 weeks. In total, 10 older adults (five females; age: 67.0 ± 6.9 years) walked onto and over six obstacles of varying heights (range: 100-200 mm) while completing no reaction time, simple reaction time, and choice reaction time tasks once per week for 5 weeks. The highest obstacles elicited the lowest toe clearance, and the first three obstacles revealed smaller heel clearance compared with the last three obstacles. Dual tasking negatively impacted obstacle clearance parameters when information processing demands were high. Longer and less consistent time to completion was observed in Session 1 compared with Sessions 2-5. Finally, improvements in simple reaction time were displayed after Session 2, but choice reaction time gradually improved and did not reach a plateau after repeated testing.

  9. Lymph node clearance of plutonium from subcutaneous wounds in beagles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dagle, G.E.

    1973-08-01

    The lymph node clearance of /sup 239/Pu O/sub 2/ administered as insoluble particles from subcutaneous implants was studied in adult beagles to simulate accidental contamination of hand wounds. External scintillation data were collected from the popliteal lymph nodes of each dog after 9.2 to 39.4 mu Ci of plutonium oxide was subcutaneously implanted into the left or right hind paws. The left hind paw was armputated 4 weeks after implantation to prevent continued deposition of plutonium oxide particles in the left popliteal lymph node. Groups of 3 dogs were sacrificed 4, 8, 16, and 32 weeks after plutonium implantation formore » histopathologic, electron microscopic, and radiochemical analysis of regional lymph nodes. An additional group of dogs received treatment with the chelating agent diethyenetriaminepentaacetic acid (DTPA). Plutonium rapidly accumulated in the popliteal lymph nodes after subcutaneous injection into the hind paw, and 1 to 10% of the implant dose was present in the popliteal lymph nodes at the time of necropsy. Histopathologic changes in the popliteal lymph nodes with plutonium particles were characterized primarily by reticular cell hyperplasia, increased numbers of macrophages, necrosis, and fibroplasia. Eventually, the plutonium particles became sequestered by scar tissue that often replaced the entire architecture of the lymph node. Light microscopic autoradiographs of the popliteal lymph nodes showed a time-related increase in number of alpha tracks per plutonium source. Electron microscopy showed that the plutonium particles were aggregated in phagolysosomes of macrophages. There was slight clearance of plutonium from the popliteal lymph nodes of dogs monitored for 32 weeks. The clearance of plutonium particles from the popliteal lymph nodes was associated with necrosis of macrophages. The external iliac lymph nodes contained fewer plutonium particles than the popliteal lymph nodes and histopathologic changes were less severe. The

  10. Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period.

    PubMed

    Saleh, J; Summers, L K; Cianflone, K; Fielding, B A; Sniderman, A D; Frayn, K N

    1998-04-01

    The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominent until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.

  11. Carbon Nanotubes in the Human Respiratory Tract-Clearance Modeling.

    PubMed

    Sturm, Robert

    2017-03-01

    Clearance of single-wall carbon nanotubes (SWCNT, diameter: 5 nm) and multi-wall carbon nanotubes (MWCNT, diameter: 50 nm) in the respiratory tract was predicted for various age groups (infants, children, adolescents, and adults). The model was founded on the assumption that lung clearance takes place in three distinct phases: (i) fast mucociliary clearance, (ii) slow bronchial clearance, and (iii) alveolar clearance. To each of these phases a specific fraction of deposited particles was attributed, the amount of which depended on particles' geometry and particles' deposition sites in the respiratory system. Clearance velocities were expressed by respective clearance half-times ranging from several hours in the case of fast clearance to tens of days in the case of slow clearance. Results of the simulations clearly demonstrate that for the specific deposition scenario (sitting, nasal breathing) considered here fast clearance fraction exhibits a slight decrease with increasing age, but total clearance times (i.e. time spans, within which 100% of the deposited particulate mass are removed) are rather constant among the age groups. Nanotubes deposited in the respiratory bronchioles and alveoli are usually subject to a long-term storage in these structures and, thus, may trigger malignant transformations in adjacent cells and tissues. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  12. Effects of airborne pollutants on mucociliary clearance.

    PubMed

    Wolff, R K

    1986-04-01

    The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposures, changes in secretions are probably responsible for most observed changes in clearance. The pollutants pertinent to this review are those that are common in the environment and most likely to have impacts on large numbers of people: sulfur oxides, sulfuric acid mist, O3, NO2, particulates, diesel exhaust, and cigarette smoke.

  13. Discounting the duration of bolus exposure in impedance testing underestimates acid reflux.

    PubMed

    Vikneswaran, Namasivayam; Murray, Joseph A

    2016-06-08

    Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH < 4) than impedance criteria (total reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH < 4) identified more studies as abnormal than MII-detected acid reflux episodes [42 vs 34 % (p < 0.01)]. Mean acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p < 0.01)], upright [58.6 s vs 13.1 s (p < 0.01)], and recumbent positions [136.7 s vs 14.2 s (p < 0.01)] with the greatest difference seen in the recumbent position. The mean ratio of mean acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position.

  14. Rapid clearance of surfactant-associated palmitic acid from the lungs of developing and adult animals.

    PubMed

    Tabor, B; Ikegami, M; Yamada, T; Jobe, A

    1990-03-01

    Palmitic acid is a minor component of natural surfactant and has been used to modify lipid extracts of natural surfactants to optimize their in vitro surface properties. The metabolic fate of palmitic acid in surfactant is unknown. The clearance of surfactant-associated radiolabeled palmitic acid after intratracheal administration was investigated with trace doses of surfactant in the adult rabbit and with trace and treatment doses in the 28-d fetal rabbit and the 132-d fetal sheep. Palmitic acid was cleared rapidly from the airways, with less than 2% of the radiolabel recovered as free palmitic acid in the alveolar wash by 1 h in all models. Recovery as free palmitic acid in the total lung at 2 h was 2% in the adult rabbit and 3% both doses in the preterm rabbit. In the preterm sheep, the recovery as free palmitic acid in the total lung was approximately 2% of the trace dose and 1% of the treatment dose by 5 h. Between 5 and 15% of the instilled palmitic acid was used as substrate for phospholipid synthesis by the lung in the different models. About 30% of the palmitate derived label was recovered in lipid extracts of liver 30 min after tracheal instillation of labeled surfactant in adult rabbits, whereas only 5-10% of the palmitate derived label was found in liver lipids in the preterm animals. In contrast to palmitic acid, radiolabeled triglyceride was cleared much more slowly from the airspaces and lungs of preterm sheep. Inasmuch as large amounts of palmitic acid are cleared rapidly from airspaces and lung tissue, it will not have a prolonged effect on the surface properties of surfactant but it may serve as a precursor for lung lipid metabolism.

  15. Red Blood Cell Membrane as a Biomimetic Nanocoating for Prolonged Circulation Time and Reduced Accelerated Blood Clearance.

    PubMed

    Rao, Lang; Bu, Lin-Lin; Xu, Jun-Hua; Cai, Bo; Yu, Guang-Tao; Yu, Xiaolei; He, Zhaobo; Huang, Qinqin; Li, Andrew; Guo, Shi-Shang; Zhang, Wen-Feng; Liu, Wei; Sun, Zhi-Jun; Wang, Hao; Wang, Tza-Huei; Zhao, Xing-Zhong

    2015-12-01

    For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have reported a phenomenon known as "accelerated blood clearance (ABC)" where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane-coated Fe(3)O(4) nanoparticles (Fe(3)O(4) @RBC NPs) rely on CD47, which is a "don't eat me" marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein-alpha (SIRP-α) receptor. Fe(3)O(4) @RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe(3)O(4) @RBC NPs does not elicit immune responses on neither the cellular level (myeloid-derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane-camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long-existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Single-sample 99mTc-diethylenetriamine penta-acetate plasma clearance in advanced renal failure by the mean sojourn time approach.

    PubMed

    Gref, Margareta C; Karp, Kjell H

    2009-03-01

    The single-sample Tc-diethylenetriamine penta-acetate (DTPA) clearance method by Christensen and Groth is recommended by the Radionuclides in Nephrourology Committee on Renal Clearance for use in adults with an estimated glomerular filtration rate (GFR) > or = 30 ml/min. The purpose of this study was to test a new Tc-DTPA single-sample low clearance formula for GFR lesser than 30 ml/min. Twenty-one adult patients (29 investigations) were included. Reference clearance was calculated with both Cr-EDTA and Tc-DTPA according to Brøchner-Mortensen with samples drawn between 3 and 24 h. Single-sample clearance was calculated from a 24 h sample using the low clearance formula(Equation is included in full-text article.) C(t) is the activity of the tracer in the plasma sample t minutes after the injection and Q0 is the injected amount. ECV is the extracellular volume in ml defined as the distribution volume of the tracer. ECV is estimated from the body surface area as ECV=8116.6xbody surface area-28.2. The mean difference between reference and Tc-DTPA single-sample clearance was -0.5 ml/min (SD 1.0 ml/min) for Tc-DTPA and -0.8 ml/min (SD 1.2 ml/min) for Cr-EDTA as reference clearance. In adult patients it is possible, even with GFR lesser than 30 ml/min, to get an accurate determination of Tc-DTPA plasma clearance from a single sample using the mean sojourn time approach. The blood sample should be obtained about 24 h after injection of the GFR tracer.

  17. Role of plaque in the clearance of salivary sucrose and its influence on salivary ph.

    PubMed

    Kumar, A; Hedge, R; Dixit, U

    2011-01-01

    The prevalence of dental caries in children, in India, is higher than many of the industrialized countries. The sugar most commonly associated with dental caries is sucrose, as the microorganisms in the dental plaque have the ability to convert this dietary constituent into various organic acids. This study was conducted to study the effect of the presence of plaque on the salivary clearance of sucrose and to study the effect of the presence of plaque on salivary pH, following sucrose clearance. Salivary sucrose determination was done by using the anthrone technique. A Digital MHOS pH meter estimated the salivary pH. Presence of plaque increased the salivary sucrose clearance time and decreased the salivary pH at various time intervals. The microbial etiology of dental caries is the dynamic relationship among the dental plaque microbiota, dietary carbohydrates, saliva and pH lowering, and the cariogenic potential of the dental plaque. Caries occur preferentially in the dentition sites characterized by high exposure to carbohydrate and diminished salivary effect.

  18. Inhibition of cytochrome P450 enzymes by saturated and unsaturated fatty acids in human liver microsomes, characterization of enzyme kinetics in the presence of bovine serum albumin (0.1 and 1.0% w/v) and in vitro - in vivo extrapolation of hepatic clearance.

    PubMed

    Palacharla, Raghava Choudary; Uthukam, Venkatesham; Manoharan, Arunkumar; Ponnamaneni, Ranjith Kumar; Padala, Nagasurya Prakash; Boggavarapu, Rajesh Kumar; Bhyrapuneni, Gopinadh; Ajjala, Devender Reddy; Nirogi, Ramakrishna

    2017-04-01

    The objective of the study was to determine the effect of fatty acids on CYP enzymes and the effect of BSA on intrinsic clearance of probe substrates. The inhibitory effect of thirteen fatty acids including saturated, mono-unsaturated and polyunsaturated fatty acids on CYP enzymes, kinetic parameters and intrinsic clearance values of nine CYP marker probe substrate reactions in the absence and presence of BSA (0.1 and 1.0% w/v) were characterized in human liver microsomes. The results demonstrate that most of the unsaturated fatty acids showed marked inhibition towards CYP2C8 mediated amodiaquine N-deethylation followed by inhibition of CYP2C9 and CYP2B6 mediated activities. The addition of 0.1% BSA in the incubation markedly improved the unbound intrinsic clearance values of probe substrates by reducing the K m values with little or no effect on maximal velocity. The addition of BSA (0.1 and 1.0% w/v) did not influence the unbound intrinsic clearance of marker reactions for CYP2A6, and CYP3A4 enzymes. The addition of 0.1% w/v BSA is sufficient to determine the intrinsic clearance of marker probe reactions by metabolite formation approach. The predicted hepatic clearance values for the substrates using the well-stirred model, in the presence of BSA (0.1% BSA), are comparable to the in vivo hepatic clearance values. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effect of time, injury, age and ethanol on interpatient variability in valproic acid pharmacokinetics after traumatic brain injury.

    PubMed

    Anderson, Gail D; Temkin, Nancy R; Awan, Asaad B; Winn, H Richard; Winn, Richard H

    2007-01-01

    Traumatic brain injury (TBI) results in an increase in hepatic metabolism. The increased metabolism is in significant contrast to a large body of in vitro and in vivo data demonstrating that activation of the host-defence response downregulates hepatic metabolism. Theoretically, this occurs because of activation of the pro-inflammatory cytokines tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-1 and IL-6. As part of a large double-blind, placebo-controlled clinical trial evaluating the use of valproic acid for prophylaxis of post-traumatic seizures, we obtained extensive valproic acid concentration-time data. Valproic acid is a hepatically metabolised, low extraction-ratio drug. Therefore, unbound clearance (CL(u)) is equal to intrinsic or metabolic clearance. The objective of this study was to evaluate the time-dependent effects of TBI on the pharmacokinetics of total and unbound valproic acid with the goal of identifying patient factors that may predict changes in total clearance (CL) and CL(u). In addition, by determining the factors that influence the magnitude and time course of induction of hepatic metabolism and understanding their interaction with the host-defence mediators, we can further our insight into the mechanism(s) responsible for the changes in CL and CL(u). Valproic acid plasma concentration data were obtained from 158 TBI patients. Unbound valproic acid plasma concentrations were estimated using total valproic acid plasma and albumin concentrations following a Scatchard equation binding model previously developed in a subset of TBI patients. The effect of 13 patient factors on CL and CL(u) was evaluated initially in a univariate analysis. The significant factors were then included in a multiple linear regression analysis by use of step-wise selection and forward selection procedures. CL and CL(u) were significantly increased after TBI in a time-dependent manner. The average increase was >75% by weeks 2 and 3 post-injury. The

  20. Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin.

    PubMed Central

    Davies, B E; Boon, R; Horton, R; Reubi, F C; Descoeudres, C E

    1988-01-01

    1. Serum concentrations of amoxycillin and clavulanic acid were measured in patients with end-stage renal disease (ESRD) following intravenous administration of 1.2 g Augmentin. Augmentin was administered on a non-dialysis day and 2 h prior to a 4 h dialysis session. 2. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for amoxycillin on the non-dialysis day were 14.4 ml min-1, 19.2 h, 14.9 l and 13.6 h, respectively. 3. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for amoxycillin were 77.1 ml min-1, 91.5 ml min-1, 0.64 and 2.30 h, respectively. 4. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for clavulanic acid on the non-dialysis day were 43.6 ml min-1, 4.4 h, 11.0 l and 3.05 h, respectively. 5. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for clavulanic acid were 92.8 ml min-1, 136 ml min-1, 0.65 and 1.19 h, respectively. 6. The total serum clearance on the non-dialysis day, which represents non-renal clearance, was lower than that in normal subjects for both amoxycillin and clavulanic acid. These data would suggest some degree of hepatic impairment in patients with ESRD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3190988

  1. Creatinine clearance test

    MedlinePlus

    Serum creatinine clearance; Kidney function - creatinine clearance; Renal function - creatinine clearance ... the body entirely by the kidneys. If kidney function is abnormal, creatinine level increases in the blood ...

  2. High-Speed, capacitance-based tip clearance sensing

    NASA Astrophysics Data System (ADS)

    Haase, W. C.; Haase, Z. S.

    This paper discusses recent advances in tip clearance measurement systems for turbine engines using capacitive probes. Real time measurements of individual blade pulses are generated using wideband signal processing providing 3 dB bandwidths of typically 5 MHz. Subsequent mixed-signal processing circuitry provide real-time measurements of maximum, minimum, and average clearance with latencies of one blade-to-blade time interval. Both guarded and unguarded probe configurations are possible with the system. Calibration techniques provide high accuracy measurements.

  3. Timing of distant flap pedicle division using xenon 133 clearance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Snelling, C.F.; Poomee, A.; Sutherland, J.B.

    1980-09-01

    Clearance of intradermally injected xenon 133 was used to measure blood flow in distant flaps in humans with the donor pedicle temporarily clamped just prior to division. All 18 flaps with a blood flow of 0.5 ml per 100 gm of tissue per minute or more survived completely after separation. Of 7 with lesser flow, 3 underwent marginal necrosis adjacent to the line of division and 4 survived entirely. Xenon 133 washout does permit quantitative evaluation of blood flow, and since it is a clean isotope, it appears superior to sodium 24 and technetium 99m, which have been used inmore » a similar manner. The test is proposed as an adjunct to clinical judgment in timing pedicle division.« less

  4. Turbine-blade tip clearance and tip timing measurements using an optical fiber bundle sensor

    NASA Astrophysics Data System (ADS)

    Garcia, Iker; Beloki, Josu; Zubia, Joseba; Durana, Gaizka; Aldabaldetreku, Gotzon

    2013-04-01

    Traditional limitations of capacitive, inductive or discharging probe sensor for tip timing and tip clearance measurements are overcome by reflective intensity modulated optical fiber sensors. This paper presents the signals and results corresponding to a one stage turbine rig which rotor has 146 blades, obtained from a transonic wind-tunnel test. The probe is based on a trifurcated bundle of optical fibers that is mounted on turbine casing. It is composed of a central illuminating fiber that guides the light from a laser to the turbine blade, and two concentric rings of receiving fibers that collect the reflected light. Two photodetectors turn this reflected light signal from the receiving rings into voltage. The electrical signals are acquired and saved by a high-sample-rate oscilloscope. In tip clearance calculations the ratio of the signals provided by each ring of receiving fibers is evaluated and translated into distance. In the case of tip timing measurements, only one of the signals is considered to get the arrival time of the blade. The differences between the real and theoretical arrival times of the blades are used to obtain the deflections amplitude. The system provides the travelling wave spectrum, which presents the average vibration amplitude of the blades at a certain nodal diameter. The reliability of the results in the turbine rig testing facilities suggests the possibility of performing these measurements in real turbines under real working conditions.

  5. Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET.

    PubMed

    de Leon, Mony J; Li, Yi; Okamura, Nobuyuki; Tsui, Wai H; Saint-Louis, Les A; Glodzik, Lidia; Osorio, Ricardo S; Fortea, Juan; Butler, Tracy; Pirraglia, Elizabeth; Fossati, Silvia; Kim, Hee-Jin; Carare, Roxana O; Nedergaard, Maiken; Benveniste, Helene; Rusinek, Henry

    2017-09-01

    Evidence supporting the hypothesis that reduced cerebrospinal fluid (CSF) clearance is involved in the pathophysiology of Alzheimer disease (AD) comes primarily from rodent models. However, unlike rodents, in which predominant extracranial CSF egress is via olfactory nerves traversing the cribriform plate, human CSF clearance pathways are not well characterized. Dynamic PET with 18 F-THK5117, a tracer for tau pathology, was used to estimate the ventricular CSF time-activity as a biomarker for CSF clearance. We tested 3 hypotheses: extracranial CSF is detected at the superior turbinates; CSF clearance is reduced in AD; and CSF clearance is inversely associated with amyloid deposition. Methods: Fifteen subjects, 8 with AD and 7 normal control volunteers, were examined with 18 F-THK5117. Ten subjects additionally underwent 11 C-Pittsburgh compound B ( 11 C-PiB) PET scanning, and 8 were 11 C-PiB-positive. Ventricular time-activity curves of 18 F-THK5117 were used to identify highly correlated time-activity curves from extracranial voxels. Results: For all subjects, the greatest density of CSF-positive extracranial voxels was in the nasal turbinates. Tracer concentration analyses validated the superior nasal turbinate CSF signal intensity. AD patients showed ventricular tracer clearance reduced by 23% and 66% fewer superior turbinate CSF egress sites. Ventricular CSF clearance was inversely associated with amyloid deposition. Conclusion: The human nasal turbinate is part of the CSF clearance system. Lateral ventricle and superior nasal turbinate CSF clearance abnormalities are found in AD. Ventricular CSF clearance reductions are associated with increased brain amyloid depositions. These data suggest that PET-measured CSF clearance is a biomarker of potential interest in AD and other neurodegenerative diseases. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  6. Fenofibrate Decreases Insulin Clearance and Insulin Secretion to Maintain Insulin Sensitivity*

    PubMed Central

    Ramakrishnan, Sadeesh K.; Russo, Lucia; Ghanem, Simona S.; Patel, Payal R.; Oyarce, Ana Maria; Heinrich, Garrett; Najjar, Sonia M.

    2016-01-01

    High fat diet reduces the expression of CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1), a transmembrane glycoprotein that promotes insulin clearance and down-regulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator-activated receptor α (PPARα) transcriptionally suppresses CEACAM1 expression, we herein examined whether high fat down-regulates CEACAM1 expression in a PPARα-dependent mechanism. By activating PPARα, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation. Despite reducing glucose-stimulated insulin secretion, fenofibrate treatment does not result in insulin insufficiency. To examine whether this is mediated by a parallel decrease in CEACAM1-dependent hepatic insulin clearance pathways, we fed wild-type and Pparα−/− null mice a high fat diet supplemented with either fenofibrate or Wy14643, a selective PPARα agonist, and examined their effect on insulin metabolism and action. We demonstrated that the decrease in insulin secretion by fenofibrate and Wy14643 is accompanied by reduction in insulin clearance in wild-type but not Pparα−/− mice, thereby maintaining normoinsulinemia and insulin sensitivity despite continuous high fat intake. Intact insulin secretion in L-CC1 mice with protected hepatic insulin clearance and CEACAM1 levels provides in vivo evidence that insulin secretion responds to changes in insulin clearance to maintain physiologic insulin and glucose homeostasis. These results also emphasize the relevant role of hepatic insulin extraction in regulating insulin sensitivity. PMID:27662905

  7. Nanoparticle-macrophage interactions: A balance between clearance and cell-specific targeting

    PubMed Central

    Rattan, Rahul; Bhattacharjee, Somnath; Zong, Hong; Swain, Corban; Siddiqui, Muneeb A.; Visovatti, Scott H.; Kanthi, Yogendra; Desai, Sajani; Pinsky, David J.; Goonewardena, Sascha N.

    2017-01-01

    The surface properties of nanoparticles (NPs) are a major factor that influences how these nanomaterials interact with biological systems. Interactions between NPs and macrophages of the reticuloendothelial system (RES) can reduce the efficacy of NP diagnostics and therapeutics. Traditionally, to limit NP clearance by the RES system, the NP surface is neutralized with molecules like poly(ethylene glycol) (PEG) which are known to resist protein adsorption and RES clearance. Unfortunately, PEG modification is not without drawbacks including difficulties with the synthesis and associations with immune reactions. To overcome some of these obstacles, we neutralized the NP surface by acetylation and compared this modification to PEGylation for RES clearance and tumor-specific targeting. We found that acetylation was comparable to PEGylation in reducing RES clearance. Additionally, we found that dendrimer acetylation did not impact folic acid (FA)-mediated targeting of tumor cells whereas PEG surface modification reduced the targeting ability of the NP. These results clarify the impact of different NP surface modifications on RES clearance and cell-specific targeting and provide insights into the design of more effective NPs. PMID:28705434

  8. Pharmacoepidemiologic investigation of clonazepam relative clearance by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients.

    PubMed

    Yukawa, Eiji; Satou, Masayasu; Nonaka, Toshiharu; Yukawa, Miho; Ohdo, Shigehiro; Higuchi, Shun; Kuroda, Takeshi; Goto, Yoshinobu

    2002-01-01

    The effects of drug-drug interactions on clonazepam clearance were examined through a retrospective analysis of serum concentration data from pediatric and adult epileptic patients. Patients received clonazepam as monotherapy or in combination with other antiepileptic drugs. A total of 259 serum clonazepam concentrations gathered from 137 patients were used in a population analysis of drug-drug interactions on clonazepam clearance. Data were analyzed using a nonlinear mixed-effects modeling (NONMEM) technique. The final model describing clonazepam clearance was CL = 152 x TBW(-0.181) x DIF, where CL is clearance (ml/kg/h), TBWis total body weight (kg), and DIF (drug interaction factor) is a scaling factor for concomitant medication with a value of 1 for patients on clonazepam monotherapy, 1.18 for those patients receiving concomitant administration of clonazepam and one antiepileptic drug (carbamazepine or valproic acid), and 2.12 x TBW(-0.119) for those patients receiving concomitant administration of clonazepam and more than two antiepileptic drugs. Clonazepam clearance decreased in a weight-related fashion in children, with minimal changes observed in adults. Concomitant administration of clonazepam and carbamazepine resulted in a 22% increase in clonazepam clearance. Concomitant administration of clonazepam and valproic acid resulted in a 12% increase in clonazepam clearance. Concomitant administration of clonazepam with two or more antiepileptic drugs resulted in a 23% to 75% increase in clonazepam clearance.

  9. Clearance of HCV RNA following acute hepatitis A superinfection.

    PubMed

    Cacopardo, B; Nunnari, G; Nigro, L

    2009-05-01

    A transient reduction of hepatitis C virus replication during the course of acute hepatitis A virus infection has already been reported in the literature. The present study reports the case study of a subject with chronic hepatitis due to hepatitis C virus who went on to develop an acute hepatitis A. From the early onset of acute disease, hepatitis C virus ribonucleic acid became undetectable. Following recovery from acute hepatitis, alanine amino-transferase levels became persistently normal and liver biopsy revealed a reduction in the Knodell histological activity index score. Hepatitis C virus ribonucleic acid clearance was maintained up to 4 years after the onset of acute hepatitis A. During the course of the acute disease, a sharp increase in interferon gamma levels was detected in serum and in the supernatant of both unstimulated and phytoemagglutinin/lipopolysaccharide-stimulated peripheral blood mononuclear cells. Interferon gamma levels were still high 3 months later. We hypothesize that acute hepatitis A virus superinfection during the course of chronic hepatitis C may lead to hepatitis C virus ribonucleic acid clearance through an immunological mechanism related to interferon gamma production.

  10. Comparison of availability and plasma clearance rates of β-hydroxy-β-methylbutyrate delivery in the free acid and calcium salt forms.

    PubMed

    Fuller, John C; Sharp, Rick L; Angus, Hector F; Khoo, Paul Y; Rathmacher, John A

    2015-11-14

    β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, has long been supplemented as a Ca salt (Ca-HMB) to increase strength and performance gains with exercise and to reduce recovery time. Recently, the free acid form of HMB (HMB-FA) has become commercially available in capsule form (gelcap). The current study was conducted to compare the bioavailability of HMB using the two commercially available capsule forms of HMB-FA and Ca-HMB. We also compared the pharmacokinetics of each form when administered mixed in water. Ten human subjects (five male and five female) were studied in a randomised crossover design. There was no significant sex by treatment interaction for any of the pharmacokinetic parameters measured. HMB-FA administered in capsules was more efficient than Ca-HMB capsule at HMB delivery with a 37 % increase in plasma clearance rate (74·8 (sem 4·0) v. 54·5 (sem 3·2) ml/min, P<0·0001) and a 76 % increase in peak plasma HMB concentration (270·2 (sem 17·8) v. 153·9 (sem 17·9) μmol/l, P<0·006), which was reached in one-third the time (P<0·009). When HMB-FA and Ca-HMB were administered in water, the differences still favoured HMB-FA, albeit to a lesser degree. Plasma HMB with HMB-FA administered in water was greater during the early phase of absorption (up to 45 min postadministration, P<0·05); this resulted in increased AUC during the first 60 min after administration, when compared with Ca-HMB mixed in water (P<0·03). In conclusion, HMB-FA in capsule form improves clearance rate and availability of HMB compared with Ca-HMB in capsule form.

  11. N-linked glycan truncation causes enhanced clearance of plasma-derived von Willebrand factor.

    PubMed

    O'Sullivan, J M; Aguila, S; McRae, E; Ward, S E; Rawley, O; Fallon, P G; Brophy, T M; Preston, R J S; Brady, L; Sheils, O; Chion, A; O'Donnell, J S

    2016-12-01

    Essentials von Willebrands factor (VWF) glycosylation plays a key role in modulating in vivo clearance. VWF glycoforms were used to examine the role of specific glycan moieties in regulating clearance. Reduction in sialylation resulted in enhanced VWF clearance through asialoglycoprotein receptor. Progressive VWF N-linked glycan trimming resulted in increased macrophage-mediated clearance. Click to hear Dr Denis discuss clearance of von Willebrand factor in a free presentation from the ISTH Academy SUMMARY: Background Enhanced von Willebrand factor (VWF) clearance is important in the etiology of both type 1 and type 2 von Willebrand disease (VWD). In addition, previous studies have demonstrated that VWF glycans play a key role in regulating in vivo clearance. However, the molecular mechanisms underlying VWF clearance remain poorly understood. Objective To define the molecular mechanisms through which VWF N-linked glycan structures influence in vivo clearance. Methods By use of a series of exoglycosidases, different plasma-derived VWF (pd-VWF) glycoforms were generated. In vivo clearance of these glycoforms was then assessed in VWF -/- mice in the presence or absence of inhibitors of asialoglycoprotein receptor (ASGPR), or following clodronate-induced macrophage depletion. Results Reduced amounts of N-linked and O-linked sialylation resulted in enhanced pd-VWF clearance modulated via ASGPR. In addition to this role of terminal sialylation, we further observed that progressive N-linked glycan trimming also resulted in markedly enhanced VWF clearance. Furthermore, these additional N-linked glycan effects on clearance were ASGPR-independent, and instead involved enhanced macrophage clearance that was mediated, at least in part, through LDL receptor-related protein 1. Conclusion The carbohydrate determinants expressed on VWF regulate susceptibility to proteolysis by ADAMTS-13. In addition, our findings now further demonstrate that non-sialic acid carbohydrate

  12. On the development of a magnetoresistive sensor for blade tip timing and blade tip clearance measurement systems

    NASA Astrophysics Data System (ADS)

    Tomassini, R.; Rossi, G.; Brouckaert, J.-F.

    2014-05-01

    The accurate control of the gap between static and rotating components is vital to preserve the mechanical integrity and ensure a correct functioning of any rotating machinery. Moreover, tip leakage above the airfoil tip results in relevant aerodynamic losses. One way to measure and to monitor blade tip gaps is by the so-called Blade Tip Clearance (BTC) technique. Another fundamental phenomenon to control in the turbomachines is the vibration of the blades. For more than half a century, this has been performed by installing strain gauges on the blades and using telemetry to transmit the signals. The Blade Tip Timing (BTT) technique, (i.e. measuring the blade time of arrival from the casing at different angular locations with proximity sensors) is currently being adopted by all manufacturers as a replacement for the classical strain gauge technique because of its non-intrusive character. This paper presents a novel magnetoresistive sensor for blade tip timing and blade tip clearance systems, which offers high temporal and high spatial resolution simultaneously. The sensing element adopted is a Wheatstone bridge of Permalloy elements. The principle of the sensor is based on the variation of magnetic field at the passage of ferromagnetic objects. Two different configurations have been realized, a digital and an analogue sensor. Measurements of tip clearance have been performed in an high speed compressor and the calibration curve is reported. Measurements of blade vibration have been carried out in a dedicated calibration bench; results are presented and discussed. The magnetoresistive sensor is characterized by high repeatability, low manufacturing costs and measurement accuracy in line with the main probes used in turbomachinery testing. The novel sensor has great potential and is capable of fulfilling the requirements for a simultaneous BTC and BTT measurement system.

  13. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion

    PubMed Central

    Butler, Judy A.; Hagen, Tory M.; Moreau, Régis

    2009-01-01

    Elevated blood triacylglycerol (TG) is a significant contributing factor to the current epidemic of obesity-related health disorders, including type-2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The observation that mice lacking the enzyme sn-glycerol-3-phosphate acyltransferase are protected from insulin resistance suggests the possibility that the regulation of TG synthesis be a target for therapy. Five-week old Zucker Diabetic Fatty (ZDF) rats were fed a diet containing (R)-α-lipoic acid (LA, ~200 mg/kg body weight per day) for 5 weeks. LA offset the rise in blood and liver TG by inhibiting liver lipogenic gene expression (e.g. sn-glycerol-3-phosphate acyltransferase-1 and diacylglycerol O-acyltransferase-2), lowering hepatic TG secretion, and stimulating clearance of TG-rich lipoproteins. LA-induced TG lowering was not due to the anorectic properties of LA, as pair-fed rats developed hypertriglyceridemia. Livers from LA-treated rats exhibited elevated glycogen content, suggesting dietary carbohydrates were stored as glycogen rather than becoming lipogenic substrate. Although AMP-activated protein kinase (AMPK) reportedly mediates the metabolic effects of LA in rodents, no change in AMPK activity was observed, suggesting LA acted independently of this kinase. The hepatic expression of peroxisome proliferator activated receptor α (PPARα) target genes involved in fatty acid β-oxidation was either unchanged or decreased with LA, indicating a different mode of action than for fibrate drugs. Given its strong safety record, LA may have potential clinical applications for the treatment or prevention of hypertriglyceridemia and diabetic dyslipidemia. PMID:19232511

  14. Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial

    PubMed Central

    Hewitt, Catherine; Hicks, Kate; Jayakody, Shalmini; Kang’ombe, Arthur Ricky; Stamuli, Eugena; Turner, Gwen; Thomas, Kim; Curran, Mike; Denby, Gary; Hashmi, Farina; McIntosh, Caroline; McLarnon, Nichola; Torgerson, David; Watt, Ian

    2011-01-01

    Objective To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts. Design A multicentre, open, two arm randomised controlled trial. Setting University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland. Participants 240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid. Interventions Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks. Main outcome measures Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment. Results There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI –8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients’ preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference –3.15% (–16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar

  15. In silico selection of therapeutic antibodies for development: Viscosity, clearance, and chemical stability

    PubMed Central

    Sharma, Vikas K.; Patapoff, Thomas W.; Kabakoff, Bruce; Pai, Satyan; Hilario, Eric; Zhang, Boyan; Li, Charlene; Borisov, Oleg; Kelley, Robert F.; Chorny, Ilya; Zhou, Joe Z.; Dill, Ken A.; Swartz, Trevor E.

    2014-01-01

    For mAbs to be viable therapeutics, they must be formulated to have low viscosity, be chemically stable, and have normal in vivo clearance rates. We explored these properties by observing correlations of up to 60 different antibodies of the IgG1 isotype. Unexpectedly, we observe significant correlations with simple physical properties obtainable from antibody sequences and by molecular dynamics simulations of individual antibody molecules. mAbs viscosities increase strongly with hydrophobicity and charge dipole distribution and decrease with net charge. Fast clearance correlates with high hydrophobicities of certain complementarity determining regions and with high positive or high negative net charge. Chemical degradation from tryptophan oxidation correlates with the average solvent exposure time of tryptophan residues. Aspartic acid isomerization rates can be predicted from solvent exposure and flexibility as determined by molecular dynamics simulations. These studies should aid in more rapid screening and selection of mAb candidates during early discovery. PMID:25512516

  16. Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia.

    PubMed

    Chuang, Yu-Chung; Chang, Shan-Chwen; Wang, Wei-Kung

    2012-08-01

    Bacteremia caused by Acinetobacter baumannii is becoming more frequent among critically ill patients, and has been associated with high mortality and prolonged hospital stay. Multidrug resistance and delay in blood culture have been shown to be significant barriers to appropriate antibiotic treatment. Quantitative polymerase chain reaction assays were recently used to monitor bacterial loads; we hypothesized that the rate of bacterial clearance determined by quantitative polymerase chain reaction can be used as a timely surrogate marker to evaluate the appropriateness of antibiotic usage. Prospective observational study. University hospital and research laboratory. Patients with culture-proven A. baumannii bacteremia in the intensive care units were prospectively enrolled from April 2008 to February 2009. Plasmid Oxa-51/pCRII-TOPO, which contained a 431-bp fragment of the A. baumannii-specific Oxa-51 gene in a pCRII-TOPO vector, was used as the standard. Sequential bacterial DNA loads in the blood were measured by a quantitative polymerase chain reaction assay. We enrolled 51 patients with A. baumannii bacteremia, and examined 318 sequential whole blood samples. The initial mean bacterial load was 2.15 log copies/mL, and the rate of bacterial clearance was 0.088 log copies/mL/day. Multivariate linear regression using the generalized estimation equation approach revealed that the use of immunosuppressants was an independent predictor for slower bacterial clearance (coefficient, 1.116; p<.001), and appropriate antibiotic usage was an independent predictor for more rapid bacterial clearance (coefficient, -0.995; p<.001). Patients with a slower rate of bacterial clearance experienced higher in-hospital mortality (odds ratio, 2.323; p=.04) Immunosuppression and appropriate antibiotic usage were independent factors affecting the rate of clearance of A. baumannii bacteremia in critical patients. These findings highlight the importance of appropriate antibiotic usage and

  17. Mechanistic investigations into the species differences in pinometostat clearance: impact of binding to alpha-1-acid glycoprotein and permeability-limited hepatic uptake.

    PubMed

    Smith, Sherri A; Gagnon, Sandra; Waters, Nigel J

    2017-03-01

    1. The plasma clearance of the first-in-class DOT1L inhibitor, EPZ-5676 (pinometostat), was shown to be markedly lower in human compared to the preclinical species, mouse, rat and dog. 2. This led to vertical allometry where various interspecies scaling methods were applied to the data, with fold-errors between 4 and 13. We had previously reported the elimination and metabolic pathways of EPZ-5676 were similar across species. Therefore, the aim of this work was to explore the mechanistic basis for the species difference in clearance for EPZ-5676, focusing on other aspects of disposition. 3. The protein binding of EPZ-5676 in human plasma demonstrated a non-linear relationship suggesting saturable binding at physiologically relevant concentrations. Saturation of protein binding was not observed in plasma from preclinical species. Kinetic determinations using purified serum albumin and alpha-1-acid glycoprotein (AAG) confirmed that EPZ-5676 is a high affinity ligand for AAG with a dissociation constant (K d ) of 0.24 μM. 4. Permeability limited uptake was also considered since hepatocyte CL int was much lower in human relative to preclinical species. Passive unbound CL int for EPZ-5676 was estimated using a correlation analysis of logD and data previously reported on seven drugs in sandwich cultured human hepatocytes. 5. Incorporation of AAG binding and permeability limited hepatic uptake into the well-stirred liver model gave rise to a predicted clearance for EPZ-5676 within 2-fold of the observed value of 1.4 mL min -1  kg -1 . This analysis suggests that the marked species difference in EPZ-5676 clearance is driven by high affinity binding to human AAG as well as species-specific hepatic uptake invoking the role of transporters.

  18. Assessment of kidney function in children by enzymatic determination of 2- or 24-h creatinine clearance: comparison with inulin clearance.

    PubMed

    Uemura, Osamu; Nagai, Takuhito; Yamakawa, Satoshi; Kaneko, Tetsuji; Hibi, Yoshiko; Yamasaki, Yasuhito; Yamamoto, Masaki; Nakano, Masaru; Iwata, Naoyuki; Hibino, Satoshi

    2016-06-01

    Although renal inulin clearance (Cin) is the gold standard for evaluation of kidney function, it cannot be measured easily. Therefore, creatinine clearance (Ccr) is often used clinically to evaluate kidney function. Enzymatically measured Ccr was recently found to be much higher than Cin because of the tubular secretion of creatinine (Cr). This study compared three measures of renal clearance, inulin, 2-h Ccr, and 24-h Ccr, in children. Kidney function was evaluated in 76 children (51 males and 25 females) aged 1 month to 18 years with chronic kidney disease (CKD) by three renal clearance methods at almost the same time. Correlations between each pair of three renal clearance measurements were determined. Approximate glomerular filtration rate (GFR) was equal to 62 % of 2-h Ccr or 76 % of 24-h Ccr. Cr secretion by renal tubules was approximately 50 % of the GFR. In this study, we indicate that the measurements of 2-h Ccr or 24-h Ccr do not show true GFR but we could infer approximate GFR from the values. The use of 2- or 24-h Ccr might contribute to the treatment of pediatric CKD patients.

  19. Allometric scaling for predicting human clearance of bisphenol A

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady statemore » volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.« less

  20. The tear turnover and tear clearance tests - a review.

    PubMed

    Garaszczuk, Izabela K; Montes Mico, Robert; Iskander, D Robert; Expósito, Alejandro Cerviño

    2018-03-01

    The aim is to provide a summary of methods available for the assessment of tear turnover and tear clearance rates. The review defines tear clearance and tear turnover and describes their implication for ocular surface health. Additionally, it describes main types of techniques for measuring tear turnover, including fluorescein tear clearance tests, techniques utilizing electromagnetic spectrum and tracer molecule and novel experimental techniques utilizing optical coherence tomography and fluorescein profilometry. Areas covered: Internet databases (PubMed, Science Direct, Google Scholar) and most frequently cited references were used as a principal resource of information on tear turnover rate and tear clearance rate, presenting methodologies and equipment, as well as their definition and implications for the anterior eye surface health and function. Keywords used for data-search were as follows: tear turnover, tear clearance, fluorescein clearance, scintigraphy, fluorophotometry, tear flow, drainage, tear meniscus dynamics, Krehbiel flow and lacrimal functional unit. Expert commentary: After decades, the topic of tear turnover assessment has been reintroduced. Recently, new techniques have been developed to propose less invasive, less time consuming and simpler methodologies for the assessment of tear dynamics that have the potential to be utilized in clinical practice.

  1. Oral sugar clearance and root caries prevalence in rheumatic patients with dry mouth symptoms.

    PubMed

    Risheim, H; Arneberg, P; Birkhed, D

    1992-01-01

    The relationship between root caries, oral sugar clearance, salivary flow rate, and salivary counts of mutans streptococci, lactobacilli and candida has been studied in a group of 22 rheumatic patients (age range 40-72 years). The study group comprised all subjects volunteering for a clinical trial on relief of dry mouth symptoms. The median salivary flow was 0.09 ml/min at rest and 0.9 ml/min during chewing stimulation. The median sugar clearance time was about 5 min in the sublingual area and 16 min in the lower buccal vestibule. For subjects with 0-2 root caries lesions the clearance time at both sites was shorter than for subjects with 3 or more lesions (p < 0.05). A long oral clearance time was significantly correlated with age, root caries (DS and DFS), low resting salivary flow, and high salivary counts of mutans streptococci. It is concluded that root caries in rheumatic patients with low salivary flow is significantly related to oral sugar clearance time.

  2. [Correlation index amylase-creatinine clearance to endogenous creatinine clearance in severe preeclampsia].

    PubMed

    Vázquez Rodríguez, Juan Gustavo; Cruz Cruz, Polita del Rocío; Márquez Hubert, Elizabeth

    2009-07-01

    Tubular lesion may cause acute renal insufficiency in pregnant patients with severe preeclampsia. To describe the correlation between the amylase/creatinine clearance ratio and endogenous creatinine depuration in pregnant patients with severe preeclampsia. Transversal study (pilot study) twenty eight women with pregnancies of 20 to 40 weeks complicated by severe preeclampsia were studied. Subjects had serum and urine creatinine and amylase determinations to calculate the amylase/creatinine clearance ratio (%). According to the results, two groups were formed: group A (> 3%) and group B (< or = 3%). The correlation between amylase/creatinine clearance ratio and endogenous creatinine depuration was evaluated. measures of central tendency and dispersion, Student's t-test, Pearson correlation coefficient (r) and linear regression were used. Group A included 23 cases (82%) and group B included 5 cases (18%). Amylase/creatinine clearance ratio (%) for group A was 5.22 +/- 1.6 and for group B was 2.41 +/- 0.41 (p = 0.001). The endogenous creatinine depuration (mL /min. /1.73 m2 SC) for group A was 105.6 +/- 9.71 and for group B was 132.10 +/- 7.95 (p = 0.54). The r between amylase/creatinine clearance ratio and endogenous creatinine depuration for group A was -0.43 and for group B was -0.25. A moderately significant negative correlation exists between amylase/creatinine clearance ratio and endogenous creatinine depuration.

  3. Effect of clearance on cartilage tribology in hip hemi-arthroplasty.

    PubMed

    Lizhang, Jia; Taylor, Simon D; Jin, Zhongmin; Fisher, John; Williams, Sophie

    2013-12-01

    Hemi-arthroplasty of the hip (an artificial femoral head articulating against the natural acetabulum) is used to treat fractured necks of femur; however, there is evidence that articulation causes erosion of the cartilage, resulting in pain for the patient. Parameters that may influence this cartilage erosion include head material and roughness, clearance between the head and acetabulum and activity levels of the patient. This study has assessed the effect of clearance of hemi-arthroplasty articulations on the contact stress, friction and cartilage deformation in an in vitro tribological simulation of the hemi-arthroplasty joint that applied dynamic loads and motion. It has been demonstrated that peak contact stress increased from 5.6 to 10.6 MPa as radial clearance increased from small (<0.6 mm) to extra-large (>1.8 mm). In all samples, friction factor increased with time and was significantly less with extra-large clearances compared to small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The cartilage deformation observed was significantly greater in acetabulum samples paired to give small or extra-large clearances compared to those with medium or large clearances.

  4. Examining Plasmodium falciparum and P. vivax clearance subsequent to antimalarial drug treatment in the Myanmar-China border area based on quantitative real-time polymerase chain reaction.

    PubMed

    Lo, Eugenia; Nguyen, Jennifer; Oo, Winny; Hemming-Schroeder, Elizabeth; Zhou, Guofa; Yang, Zhaoqing; Cui, Liwang; Yan, Guiyun

    2016-04-16

    Recent emergence of artemisinin-resistant P. falciparum has posed a serious hindrance to the elimination of malaria in the Greater Mekong Subregion. Parasite clearance time, a measure of change in peripheral parasitaemia in a sequence of samples taken after treatment, can be used to reflect the susceptibility of parasites or the efficiency of antimalarials. The association of genetic polymorphisms and artemisinin resistance has been documented. This study aims to examine clearance time of P. falciparum and P. vivax parasitemia as well as putative gene mutations associated with residual or recurred parasitemia in Myanmar. A total of 63 P. falciparum and 130 P. vivax samples collected from two internally-displaced populations and one surrounding village were examined for parasitemia changes. At least four samples were taken from each patient, at the first day of diagnosis up to 3 months following the initial treatment. The amount of parasite gene copy number was estimated using quantitative real-time PCR based on a species-specific region of the 18S rRNA gene. For samples that showed residual or recurred parasitemia after treatment, microsatellites were used to identify the 'post-treatment' parasite genotype and compared such with the 'pre-treatment' genotype. Mutations in genes pfcrt, pfmdr1, pfatp6, pfmrp1 and pfK13 that are potentially associated with ACT resistance were examined to identify if mutation is a factor for residual or persistent parasitemia. Over 30% of the P. falciprium infections showed delayed clearance of parasitemia after 2-3 days of treatment and 9.5% showed recurred parasitemia. Mutations in codon 876 of the pfmrp1 corroborated significance association with slow clearance time. However, no association was observed in the variation in pfmdr1 gene copy number as well as mutations of various codonsinpfatp6, pfcrt, and pfK13 with clearance time. For P. vivax, over 95% of the infections indicated cleared parasitemia at days 2-3 of treatment. Four

  5. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

  6. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

  7. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

  8. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

  9. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

  10. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

  11. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Propeller clearance. 25.925 Section 25.925... STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances with the airplane at maximum weight, with the most adverse...

  12. 14 CFR 23.925 - Propeller clearance.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Propeller clearance. 23.925 Section 23.925... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless smaller clearances are substantiated, propeller clearances, with the airplane at the most...

  13. Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention.

    PubMed

    Henriksen, Ulrik L; Hansen, Hanne B; Ring-Larsen, Helmer; Bendtsen, Flemming; Henriksen, Jens H

    2015-01-01

    In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients with cirrhosis with and without fluid retention. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 mL/min/1.73 m(2). In patients with ascites, ClΔ was significantly higher (17.6 mL/min/1.73 m(2), p < 0.0001). ClΔ increased with lower values of GFR (r = - 0.458, p < 0.001). Repeated measurements of ClU in a subgroup of patients with fluid retention (n = 25) gave almost identical values. Different types of corrections of one-pool clearance were almost identical with ClP, except for higher clearance values, which were somewhat underestimated by the former. In patients with fluid retention and ascites ClP and corrected one-pool clearance overestimates GFR substantially. Although ClU may underestimate GFR slightly, patients with ascites should collect urine quantitatively in order to obtain a reliable measurement of GFR.

  14. Test Rig for Evaluating Active Turbine Blade Tip Clearance Control Concepts

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Steinetz, Bruce M.; Robbie, Malcolm G.

    2003-01-01

    Improved blade tip sealing in the high pressure compressor and high pressure turbine can provide dramatic improvements in specific fuel consumption, time-on-wing, compressor stall margin and engine efficiency as well as increased payload and mission range capabilities of both military and commercial gas turbine engines. The preliminary design of a mechanically actuated active clearance control (ACC) system for turbine blade tip clearance management is presented along with the design of a bench top test rig in which the system is to be evaluated. The ACC system utilizes mechanically actuated seal carrier segments and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. The purpose of this active clearance control system is to improve upon current case cooling methods. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, re-burst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). The active turbine blade tip clearance control system design presented herein will be evaluated to ensure that proper response and positional accuracy is achievable under simulated high-pressure turbine conditions. The test rig will simulate proper seal carrier pressure and temperature loading as well as the magnitudes and rates of blade tip clearance changes of an actual gas turbine engine. The results of these evaluations will be presented in future works.

  15. Measurement of Rotating Blade Tip Clearance with Fibre-Optic Probe

    NASA Astrophysics Data System (ADS)

    Cao, S. Z.; Duan, F. J.; Zhang, Y. G.

    2006-10-01

    This paper described a tip clearance measuring system with fibre-optic probe. The system is based on a novel tip clearance sensor of optical fibre-bundle mounted on the casing, rotating speed synchronization sensor mounted on the rotating shaft, the tip clearance preamplification processing circuit followed by high speed data-acquisition unit. A novel tip clearance sensor of trifurcated optical fibre bundle was proposed and demonstrated. It is independent of material of measured surface but capacitive probe demands target conductive. Measurements can be taken under severe conditions such as ionization. Sensor circuitry and data acquisition circuit were successfully designed. With the help of Rotation synchronized sensor, all the blades can be detected in real-time. Because of fibre-optic sensor, the measuring system has commendably frequency response, which can work well in high rotating speed from 0-15000rpm.The measurement range of tip clearance is 0-3mm with 25um precision.

  16. Experimental models for studying mucociliary clearance.

    PubMed

    King, M

    1998-01-01

    Respiratory tract mucus is a viscoelastic gel, the rheological properties of which are determined mainly by its content of mucous glycoproteins and water. The rheology and quantity of mucus, in concert with ciliary factors, are the major determinants of mucociliary clearance. A wide range of animal models for studying the secretion and clearance of mucus are available. Ex vivo models, such as the frog palate or excised bovine trachea, provide direct, meaningful data regarding the clearability of mucus. Rodent models of chronic bronchitis, based on irritant gas or cigarette smoke exposure, show important features of the human condition in a relatively short time. The rheological characterization of mucus is made difficult by the small quantities obtainable, particularly from normal animals. Large animal models, such as the dog or sheep, although more expensive, offer many advantages, such as the ability to carry out long-term serial measurements, and to make integrated measurements of the clearance of mucus, ciliary function, epithelial ion transport, and the rheology of mucus in the same preparation.

  17. Fiber-optic laser Doppler turbine tip clearance probe

    NASA Astrophysics Data System (ADS)

    Büttner, Lars; Pfister, Thorsten; Czarske, Jürgen

    2006-05-01

    A laser Doppler based method for in situ single blade tip clearance measurements of turbomachines with high precision is presented for what we believe is the first time. The sensor is based on two superposed fanlike interference fringe systems generated by two laser wavelengths from a fiber-coupled, passive, and therefore compact measurement head employing diffractive optics. Tip clearance measurements at a transonic centrifugal compressor performed during operation at 50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured uncertainty of the tip position was less than 20 μm, a factor of 2 more accurate than that of capacitive probes. The sensor offers great potential for in situ and online high-precision tip clearance measurements of metallic and nonmetallic turbine blades.

  18. Fiber-optic laser Doppler turbine tip clearance probe.

    PubMed

    Büttner, Lars; Pfister, Thorsten; Czarske, Jürgen

    2006-05-01

    A laser Doppler based method for in situ single blade tip clearance measurements of turbomachines with high precision is presented for what we believe is the first time. The sensor is based on two superposed fanlike interference fringe systems generated by two laser wavelengths from a fiber-coupled, passive, and therefore compact measurement head employing diffractive optics. Tip clearance measurements at a transonic centrifugal compressor performed during operation at 50,000 rpm (833 Hz, 586 m/s tip speed) are reported. At these speeds the measured uncertainty of the tip position was less than 20 microm, a factor of 2 more accurate than that of capacitive probes. The sensor offers great potential for in situ and online high-precision tip clearance measurements of metallic and nonmetallic turbine blades.

  19. Turbine blade tip clearance measurement using a skewed dual-beam fiber optic sensor

    NASA Astrophysics Data System (ADS)

    Ye, De-chao; Duan, Fa-jie; Guo, Hao-tian; Li, Yangzong; Wang, Kai

    2012-08-01

    Optimization and active control of the tip clearance of turbine blades has been identified as a key to improve fuel efficiency, reduce emission, and increase service life of the engine. However, reliable and real-time tip clearance measurement is difficult due to the adverse environmental conditions that are typically found in a turbine. We describe a dual-beam fiber optic measurement system that can measure the tip timing and tip clearance simultaneously. Because the tip timing information is used to calculate the tip clearance, the method is insensitive to the signal intensity variation caused by fluctuations in environmental conditions such as light source instability, contamination, and blade tip imperfection. The system was calibrated and tested using experimental rotors. The test results indicated a high resolution of 4.5 μm and measurement accuracy of ±20 μm over the rotation speed range of 2000 to 10,000 rpm.

  20. Estimation of residual glomerular filtration rate in peritoneal dialysis patients using cystatin C: comparison with 51Cr-EDTA clearance.

    PubMed

    Carter, Joanne L; Lane, Catherine E; Fan, Stanley L; Lamb, Edmund J

    2011-11-01

    Measuring glomerular filtration rate (GFR) is an important assessment in peritoneal dialysis patients. In clinical practice, it is commonly measured by calculating the mean of the urinary clearance of urea and creatinine (GFR(UrCl)) but this process is time consuming and unreliable. We wished to compare several estimates of GFR including residual GFR estimated from cystatin C (GFR(CysC)) using a published equation (Hoek), GFR(UrCl) and (51)Cr-ethylenediaminetetraacetic acid (EDTA) clearance, in peritoneal dialysis patients. GFR(CysC), GFR(UrCl) and (51)Cr-EDTA clearance were measured in 28 patients undergoing peritoneal dialysis in a single dialysis unit. GFR(CysC) was related to GFR(UrCl) (Spearman's rank correlation coefficient r(s) = 0.44; P = 0.0185) and to (51)Cr-EDTA clearance (r(s) = 0.48; P = 0.0099). GFR(CysC) values were significantly (P = 0.0077) lower than (51)Cr-EDTA clearance results (mean bias -19.7%). However, GFR(CysC) did not differ significantly (P > 0.05) from GFR(UrCl). GFR(CysC) is related to GFR(UrCl) but has a significant negative bias against (51)Cr-EDTA. Given the known limitations of (51)Cr-EDTA in estimating GFR in renal failure, this study provides additional validation suggesting that cystatin C-estimated rGFR (GFR(CysC)) gives a reasonable estimation of GFR without the clinical problems associated with 24 h urine collections.

  1. Depressed reticuloendothelial clearance of platelets in rats after trauma.

    PubMed

    Kaplan, J E; Moon, D G; Minnear, F L; Saba, T M

    1984-02-01

    Platelet microembolization may contribute to microcirculatory and organ damage following trauma and shock. It is hypothesized that posttraumatic reticuloendothelial depression predisposes to such microembolization by failure to clear altered platelets from the circulation. The present study evaluated the short-term (1 h) clearance and organ localization of radiolabeled homologous damaged platelets in normal rats and in rats following sublethal Noble-Collip drum trauma. Platelets were collected in citrated platelet-rich plasma from normal rats and labeled with 51Cr in citrated saline. Platelets were altered by repeated centrifugation in protein-free medium. These platelets differed functionally and morphologically from normal platelets. Disappearance of iv injected damaged platelets conformed to a two-compartment exponential clearance. Velocity of clearance in the rapid compartment correlated with hepatic platelet localization, whereas velocity of clearance in the second compartment correlated with splenic platelet localization. Clearance rate of the rapid compartment was depressed at 1 h after trauma and elevated at 24 h. These changes were associated with a decrease in hepatic platelet localization at 1 h and an increase above normal at 24 h. Splenic platelet localization was decreased by 3 h following trauma. Pulmonary platelet localization was increased at all times following trauma. It is concluded that the posttrauma state is associated with a defect in the reticuloendothelial system clearance of altered platelets, which may augment embolization of platelets in the lung.

  2. Simple geometric algorithms to aid in clearance management for robotic mechanisms

    NASA Technical Reports Server (NTRS)

    Copeland, E. L.; Ray, L. D.; Peticolas, J. D.

    1981-01-01

    Global geometric shapes such as lines, planes, circles, spheres, cylinders, and the associated computational algorithms which provide relatively inexpensive estimates of minimum spatial clearance for safe operations were selected. The Space Shuttle, remote manipulator system, and the Power Extension Package are used as an example. Robotic mechanisms operate in quarters limited by external structures and the problem of clearance is often of considerable interest. Safe clearance management is simple and suited to real time calculation, whereas contact prediction requires more precision, sophistication, and computational overhead.

  3. Comparing taxi clearance input layouts for advancements in flight deck automation for surface operations

    NASA Astrophysics Data System (ADS)

    Cheng, Lara W. S.

    Airport moving maps (AMMs) have been shown to decrease navigation errors, increase taxiing speed, and reduce workload when they depict airport layout, current aircraft position, and the cleared taxi route. However, current technologies are limited in their ability to depict the cleared taxi route due to the unavailability of datacomm or other means of electronically transmitting clearances from ATC to the flight deck. This study examined methods by which pilots can input ATC-issued taxi clearances to support taxi route depictions on the AMM. Sixteen general aviation (GA) pilots used a touchscreen monitor to input taxi clearances using two input layouts, softkeys and QWERTY, each with and without feedforward (graying out invalid inputs). QWERTY yielded more taxi route input errors than the softkeys layout. The presence of feedforward did not produce fewer taxi route input errors than in the non-feedforward condition. The QWERTY layout did reduce taxi clearance input times relative to the softkeys layout, but when feedforward was present this effect was observed only for the longer, 6-segment taxi clearances. It was observed that with the softkeys layout, feedforward reduced input times compared to non-feedforward but only for the 4-segment clearances. Feedforward did not support faster taxi clearance input times for the QWERTY layout. Based on the results and analyses of the present study, it is concluded that for taxi clearance inputs, (1) QWERTY remain the standard for alphanumeric inputs, and (2) feedforward be investigated further, with a focus on participant preference and performance of black-gray contrast of keys.

  4. Estradiol and weight are covariates of paracetamol clearance in young women.

    PubMed

    Beleyn, B; Vermeersch, S; Kulo, A; Smits, A; Verbesselt, R; de Hoon, J N; Van Calsteren, K; Allegaert, K

    2014-01-01

    Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored. In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m(2)) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence. Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m(2), at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001). Estradiol and weight in part explain the variation in paracetamol clearance in young women. © 2014 S. Karger AG, Basel.

  5. UXO clearance operation in Laos

    NASA Astrophysics Data System (ADS)

    Sato, Motoyuki; Kadoya, Yoshihiko

    2018-04-01

    Laos is one of the most seriously contaminated countries by UXO. Most of the UXO are cluster bombs, used in 1960- 70's. There is historical political background about the UXO problems in Laos. Currently, The clearance of UXO is significantly important for future economic development for Laos. It affects not only local inhabitants, but it will affects national economy. For example, UXO clearance in mountainous area can promote construction of roads, and Laos has a good possibility to be the center of transportation in Indo-Chia region. We have started a research project for evaluation of impact of UXO clearance in Laos, "The economic impact and the technological development for the elimination of unexploded ordnance (UXO) elimination in Laos". Lao National Unexploded Ordnance Programme (UXO Lao) is working in the nine most impacted provinces nationwide and it clears land for agriculture and community purposes. We recently visited Laos and observed the UXO clearance procedure conducted by UXOLAO. The technical survey for UXO clearance site to determine for operation, UXO detection by using metal detectors are organized by UXO Lao. In this paper, we will report the technical aspects of the UXO clearance in Laos.

  6. Free acid gel form of β-hydroxy-β-methylbutyrate (HMB) improves HMB clearance from plasma in human subjects compared with the calcium HMB salt.

    PubMed

    Fuller, John C; Sharp, Rick L; Angus, Hector F; Baier, Shawn M; Rathmacher, John A

    2011-02-01

    The leucine metabolite, β-hydroxy-β-methylbutyrate (HMB), is a nutritional supplement that increases lean muscle and strength with exercise and in disease states. HMB is presently available as the Ca salt (CaHMB). The present study was designed to examine whether HMB in free acid gel form will improve HMB availability to tissues. Two studies were conducted and in each study four males and four females were given three treatments in a randomised, cross-over design. Treatments were CaHMB (gelatin capsule, 1 g), equivalent HMB free acid gel swallowed (FASW) and free acid gel held sublingual for 15 s then swallowed (FASL). Plasma HMB was measured for 3 h following treatment in study 1 and 24 h with urine collection in study 2. In both the studies, the times to peak plasma HMB were 128 (sem 11), 38 (sem 4) and 38 (sem 1) min (P < 0·0001) for CaHMB, FASW and FASL, respectively. The peak concentrations were 131 (sem 6), 249 (sem 14) and 239 (sem 14) μmol/l (P < 0·0001) for CaHMB, FASW and FASL, respectively. The areas under the curve were almost double for FASW and FASL (P < 0·0001). Daily urinary HMB excretion was not significantly increased resulting in more HMB retained (P < 0·003) with FASW and FASL. Half-lives were 3·17 (sem 0·22), 2·50 (sem 0·13) and 2·51 (sem 0·14) h for CaHMB, FASW and FASL, respectively (P < 0·004). Free acid gel resulted in quicker and greater plasma concentrations (+185%) and improved clearance (+25%) of HMB from plasma. In conclusion, HMB free acid gel could improve HMB availability and efficacy to tissues in health and disease.

  7. Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals

    PubMed Central

    de Albuquerque, Isabella Martins; Cardoso, Dannuey Machado; Masiero, Paulo Ricardo; Paiva, Dulciane Nunes; Resqueti, Vanessa Regiane; Fregonezi, Guilherme Augusto de Freitas; Menna-Barreto, Sérgio Saldanha

    2016-01-01

    ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. PMID:28117469

  8. Evaluation of lung clearance of inhaled pertechnegas.

    PubMed

    Fanti, S; Compagnone, G; Pancaldi, D; Franchi, R; Corbelli, C; Marengo, M; Onofri, C; Galassi, R; Levorato, M; Monetti, N

    1996-02-01

    Pertechnegas is a new ventilation agent produced by modifying the atmosphere of combustion of Technegas. Due to its rapid disappearance from the lungs, Pertechnegas has been suggested as useful in measuring pulmonary epithelial permeability. This study aimed to assess the reliability of ventilation scans with Pertechnegas to evaluate alveolar-capillary permeability. Six non-smokers with no evidence of pulmonary disease were investigated. Scintigraphic data were used to evaluate the site of Pertechnegas deposition (by assessing the Penetration Index [PI] of the gas), its clearance rate (by calculating the time to half-clearance [T1/2]) and its lung distribution (by means of a pixel-by-pixel analysis. PI measurements produced a mean value of 88.8 +/- 13.3% (range 69-117%). Time activity curves showed a fast clearance in all cases (mean T1/2 = 10.7 +/- 2.1 min, range 8.1-14.3 min). Comparison of statistical indices of uniform deposition (skewness and kurtosis) indicated satisfactory homogeneity of Pertechnegas distribution throughout the lungs. These data show that after inhalation Pertechnegas has a peripheral deposition and a homogeneous distribution in the lungs and is rapidly cleared through the alveolar-capillary barrier. In conclusion Pertechnegas can be recommended as a potential radiopharmaceutical for studying the pulmonary epithelial barrier.

  9. On the development of a magnetoresistive sensor for blade tip timing and blade tip clearance measurement systems.

    PubMed

    Tomassini, R; Rossi, G; Brouckaert, J-F

    2016-10-01

    A simultaneous blade tip timing (BTT) and blade tip clearance (BTC) measurement system enables the determination of turbomachinery blade vibrations and ensures the monitoring of the existing running gaps between the blade tip and the casing. This contactless instrumentation presents several advantages compared to the well-known telemetry system with strain gauges, at the cost of a more complex data processing procedure. The probes used can be optical, capacitive, eddy current as well as microwaves, everyone with its dedicated electronics and many existing different signal processing algorithms. Every company working in this field has developed its own processing method and sensor technology. Hence, repeating the same test with different instrumentations, the answer is often different. Moreover, rarely it is possible to achieve reliability for in-service measurements. Developments are focused on innovative instrumentations and a common standard. This paper focuses on the results achieved using a novel magnetoresistive sensor for simultaneous tip timing and tip clearance measurements. The sensor measurement principle is described. The sensitivity to gap variation is investigated. In terms of measurement of vibrations, experimental investigations were performed at the Air Force Institute of Technology (ITWL, Warsaw, Poland) in a real aeroengine and in the von Karman Institute (VKI) R2 compressor rig. The advantages and limitations of the magnetoresistive probe for turbomachinery testing are highlighted.

  10. On the development of a magnetoresistive sensor for blade tip timing and blade tip clearance measurement systems

    NASA Astrophysics Data System (ADS)

    Tomassini, R.; Rossi, G.; Brouckaert, J.-F.

    2016-10-01

    A simultaneous blade tip timing (BTT) and blade tip clearance (BTC) measurement system enables the determination of turbomachinery blade vibrations and ensures the monitoring of the existing running gaps between the blade tip and the casing. This contactless instrumentation presents several advantages compared to the well-known telemetry system with strain gauges, at the cost of a more complex data processing procedure. The probes used can be optical, capacitive, eddy current as well as microwaves, everyone with its dedicated electronics and many existing different signal processing algorithms. Every company working in this field has developed its own processing method and sensor technology. Hence, repeating the same test with different instrumentations, the answer is often different. Moreover, rarely it is possible to achieve reliability for in-service measurements. Developments are focused on innovative instrumentations and a common standard. This paper focuses on the results achieved using a novel magnetoresistive sensor for simultaneous tip timing and tip clearance measurements. The sensor measurement principle is described. The sensitivity to gap variation is investigated. In terms of measurement of vibrations, experimental investigations were performed at the Air Force Institute of Technology (ITWL, Warsaw, Poland) in a real aeroengine and in the von Karman Institute (VKI) R2 compressor rig. The advantages and limitations of the magnetoresistive probe for turbomachinery testing are highlighted.

  11. Impairment of aminopyrine clearance in aspirin-damaged canine gastric mucosa

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Miller, T.A.; Henagan, J.M.; Loy, T.M.

    Using an in vivo canine chambered stomach preparation, the clearance of (/sup 14/C)aminopyrine across mucosa when intravenously infused and the back-diffusion of this substance from gastric lumen to mucosa when topically applied to gastric epithelium were evaluated in aspirin-damaged gastric epithelium. In mucosa damaged by either 20 mM or 40 mM aspirin, the recovery of (/sup 14/C)aminopyrine, when topically mixed with acid (pH . 1.1) perfusate solution, was not significantly different from nondamaged control mucosa. In addition, the degree of ''trapping'' of this substance from back-diffusion was not different in damaged mucosa from that observed in nondamaged epithelium. In contrast,more » when (/sup 14/C)aminopyrine was intravenously infused, its clearance was significantly impaired in aspirin-damaged mucosa when compared with control studies, as evidenced by the increased ''trapping'' of this substance in injured epithelium. These findings indicate that movement of aminopyrine from plasma to gastric lumen is impaired in damaged epithelium, making the aminopyrine clearance technique an unreliable method to accurately measure absolute gastric blood flow in this experimental setting.« less

  12. PINK1 is required for timely cell-type specific mitochondrial clearance during Drosophila midgut metamorphosis.

    PubMed

    Liu, Yan; Lin, Jingjing; Zhang, Minjie; Chen, Kai; Yang, Shengxi; Wang, Qun; Yang, Hongqin; Xie, Shusen; Zhou, Yongjian; Zhang, Xi; Chen, Fei; Yang, Yufeng

    2016-11-15

    Mitophagy is the selective degradation of mitochondria by autophagy, which is an important mitochondrial quality and quantity control process. During Drosophila metamorphosis, the degradation of midgut involves a large change in length and organization, which is mediated by autophagy. Here we noticed a cell-type specific mitochondrial clearance process that occurs in enterocytes (ECs), while most mitochondria remain in intestinal stem cells (ISCs) during metamorphosis. Although PINK1/PARKIN represent the canonical pathway for the elimination of impaired mitochondria in varied pathological conditions, their roles in developmental processes or normal physiological conditions have been less studied. To examine the potential contribution of PINK1 in developmental processes, we monitored the dynamic expression pattern of PINK1 in the midgut development by taking advantage of a newly CRISPR/Cas9 generated knock-in fly strain expressing PINK1-mCherry fusion protein that presumably recapitulates the endogenous expression pattern of PINK1. We disclosed a spatiotemporal correlation between the expression pattern of PINK1 and the mitochondrial clearance or persistence in ECs or ISCs respectively. By mosaic genetic analysis, we then demonstrated that PINK1 and PARKIN function epistatically to mediate the specific timely removal of mitochondria, and are involved in global autophagy in ECs during Drosophila midgut metamorphosis, with kinase-dead PINK1 exerting dominant negative effects. Taken together, our studies concluded that the PINK1/PARKIN is crucial for timely cell-type specific mitophagy under physiological conditions and demonstrated again that Drosophila midgut metamorphosis might serve as an elegant in vivo model to study autophagy. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Pharmacokinetics of tolfenamic acid and its detection time in urine after intravenous administration of the drug in camels (Camelus dromedarius).

    PubMed

    Wasfi, I A; ElGhazali, M; Hadi, A A; Zorob, O; Boni, N S; Alkatheeri, N A; Barezaiq, I M

    1998-11-01

    To document tolfenamic acid disposition variables, identify its major phase-1 metabolite and fragmentation pattern, and establish detection time in urine after single IV bolus administration to make recommendations on avoiding violative residues in racing camels. 7 healthy camels (6 males, 1 female), 8 to 11 years old and weighing from 300 to 480 kg. Blood samples were collected at 0, 5, 10, 15, 30, 45, and 60 minutes and at 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 13, 14, 15, and 16 hours after IV administration of tolfenamic acid (2.0 mg/kg of body weight). Urine samples were collected daily for 14 days after drug administration. Serum tolfenamic acid concentration was measured; limit of quantification was 50 ng/ml. A metabolite of tolfenamic acid in urine was isolated and identified, and its major fragmentation pattern was verified. Screening for tolfenamic acid and its metabolite in urine was performed. Mean +/- SEM tolfenamic acid elimination half-life was 5.76+/-0.26 hours. Total body clearance was 0.109+/-0.011 L/kg/h, and steady-state volume of distribution was 0.68+/-0.06 L/kg. Detection time for tolfenamic acid and its hydroxylated metabolite in urine after IV administration of a dose of 2.0 mg/kg was 5 and 7 days, respectively. Camels eliminate tolfenamic acid mainly via metabolism more slowly than do cattle. The extrapolated dose regimen from cattle to camels appears inappropriate. Veterinarians are advised not to use tolfenamic acid in camels for at least 8 days prior to racing.

  14. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

  15. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

  16. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor...

  17. Renal Clearance: Using an Interactive Activity to Visualize a Tricky Concept

    ERIC Educational Resources Information Center

    Hull, Kerry

    2016-01-01

    Renal clearance, the volume of blood cleared of a substance in a particular time period, is commonly recognized as one of the most difficult concepts in physiology. This difficulty may in part reflect the quantitative nature of renal clearance since many life sciences majors perceive that mathematics is irrelevant to their discipline. Students may…

  18. CO2 clearance by membrane lungs.

    PubMed

    Sun, Liqun; Kaesler, Andreas; Fernando, Piyumindri; Thompson, Alex J; Toomasian, John M; Bartlett, Robert H

    2018-05-01

    Commercial membrane lungs are designed to transfer a specific amount of oxygen per unit of venous blood flow. Membrane lungs are much more efficient at removing CO 2 than adding oxygen, but the range of CO 2 transfer is rarely reported. Commercial membrane lungs were studied with the goal of evaluating CO 2 removal capacity. CO 2 removal was measured in 4 commercial membrane lungs under standardized conditions. CO 2 clearance can be greater than 4 times that of oxygen at a given blood flow when the gas to blood flow ratio is elevated to 4:1 or 8:1. The CO 2 clearance was less dependent on surface area and configuration than oxygen transfer. Any ECMO system can be used for selective CO 2 removal.

  19. Impact of high-flux haemodialysis on the probability of target attainment for oral amoxicillin/clavulanic acid combination therapy.

    PubMed

    Hui, Katrina; Patel, Kashyap; Kong, David C M; Kirkpatrick, Carl M J

    2017-07-01

    Clearance of small molecules such as amoxicillin and clavulanic acid is expected to increase during high-flux haemodialysis, which may result in lower concentrations and thus reduced efficacy. To date, clearance of amoxicillin/clavulanic acid (AMC) during high-flux haemodialysis remains largely unexplored. Using published pharmacokinetic parameters, a two-compartment model with first-order input was simulated to investigate the impact of high-flux haemodialysis on the probability of target attainment (PTA) of orally administered AMC combination therapy. The following pharmacokinetic/pharmacodynamic targets were used to calculate the PTA. For amoxicillin, the time that the free concentration remains above the minimum inhibitory concentration (MIC) of ≥50% of the dosing period (≥50%ƒT >MIC ) was used. For clavulanic acid, the time that the free concentration was >0.1 mg/L of ≥45% of the dosing period (≥45%ƒT >0.1 mg/L ) was used. Dialysis clearance reported in low-flux haemodialysis for both compounds was doubled to represent the likely clearance during high-flux haemodialysis. Monte Carlo simulations were performed to produce concentration-time profiles over 10 days in 1000 virtual patients. Seven different regimens commonly seen in clinical practice were explored. When AMC was dosed twice daily, the PTA was mostly ≥90% for both compounds regardless of when haemodialysis commenced. When administered once daily, the PTA was 20-30% for clavulanic acid and ≥90% for amoxicillin. The simulations suggest that once-daily orally administered AMC in patients receiving high-flux haemodialysis may result in insufficient concentrations of clavulanic acid to effectively treat infections, especially on days when haemodialysis occurs. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  20. Stable isotope labeling tandem mass spectrometry (SILT) to quantify protein production and clearance rates

    PubMed Central

    Bateman, Randall J.; Munsell, Ling Y.; Chen, Xianghong; Holtzman, David M.; Yarasheski, Kevin E.

    2007-01-01

    In all biological systems, protein amount is a function of the rate of production and clearance. The speed of a response to a disturbance in protein homeostasis is determined by turnover rate. Quantifying alterations in protein synthesis and clearance rates is vital to understanding disease pathogenesis (e.g., aging, inflammation). No methods exist for quantifying production and clearance rates of low abundance (femtomole) proteins in vivo. We describe a novel, mass spectrometry-based method for quantitating low abundance protein synthesis and clearance rates in vitro and in vivo in animals and humans. The utility of this method is demonstrated with amyloid-beta (Aß), an important low abundance protein involved in Alzheimer's disease pathogenesis. We used in vivo stable isotope labeling, immunoprecipitation of Aß from cerebrospinal fluid, and quantitative liquid chromatography electrospray-ionization tandem mass spectrometry (LC-ESI-tandem MS) to quantify human Aß protein production and clearance rates. The method is sensitive and specific for stable isotope labeled amino acid incorporation into CNS (± 1% accuracy). This in vivo method can be used to identify pathophysiologic changes in protein metabolism; and may serve as a biomarker for monitoring disease risk, progression, or response to novel therapeutic agents. The technique is adaptable to other macromolecules, such as carbohydrates or lipids. PMID:17383190

  1. Extended reuse of polysulfone hemodialysis membranes using citric acid and heat.

    PubMed

    Tonelli, Marcello; Dymond, Clayton; Gourishankar, Sita; Jindal, Kailash K

    2004-01-01

    The concomitant use of citric acid and prolonged exposure to heat (CAH) is an increasingly common alternative to purely chemical means of reusing dialyzers. However, there are no data on the effects of reprocessing dialyzers with CAH beyond 15 uses. Increasing the number of reuses with CAH cannot be systematically undertaken unless its safety is documented. We hypothesized that discarding polysulfone dialyzers after the 25th rather than the 15th use would result in increased clearance of beta2-microglobulin (beta2MG) without clinically significant changes in small solute clearance or albumin loss. We studied 15 Fresenius F80B polysulfone dialyzers in five chronic hemodialysis patients. Dialyzers were reprocessed using 1.5% citric acid solution heated to 95 degrees C. Representative fractional collection and 10 minute timed collections of dialysate were performed at baseline and during uses 5, 10, 15, 20, and 25 for each dialyzer. Dialysate-side urea, creatinine, and beta2MG clearances were calculated, and total albumin was measured in dialysate. We used a mixed model to adjust for repeated measures (both within a given dialyzer and for the multiple dialyzers per patient). Of the 15 dialyzers studied, 3 (20%) failed before the 25th use. There was no significant change in urea or creatinine clearance with additional reuse (overall p values 0.20 and 0.60, respectively). A sustained increase in beta2MG clearance was observed after the fifth treatment compared with the first use (p < 0.001). Fractional collection showed that dialysate albumin loss increased significantly with additional reuses (p < 0.001) but did not increase significantly above baseline until treatment 25. Reprocessing of polysulfone dialyzers with CAH 25 times significantly increased albumin loss and beta2MG clearance but did not appear to affect urea or creatinine clearance. Increasing the maximum number of uses to 20 may permit cost savings compared with current practice without additional risk.

  2. Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

    PubMed

    Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

    2017-01-17

    Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p <2 × 10 -6 ) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10 -7 . We observed a strong association (p < 8 × 10 -8 ) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

  3. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

  4. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

  5. 22 CFR 16.6 - Security clearances.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Security clearances. 16.6 Section 16.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL FOREIGN SERVICE GRIEVANCE SYSTEM § 16.6 Security clearances. The agencies shall use their best endeavors to expedite security clearances whenever necessary to ensure a fair...

  6. Blood lactate clearance after maximal exercise depends on active recovery intensity.

    PubMed

    Devlin, J; Paton, B; Poole, L; Sun, W; Ferguson, C; Wilson, J; Kemi, O J

    2014-06-01

    High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise. We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration>10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold. Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05). Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold.

  7. Secretion clearance strategies in Australian and New Zealand Intensive Care Units.

    PubMed

    Ntoumenopoulos, George; Hammond, Naomi; Watts, Nicola R; Thompson, Kelly; Hanlon, Gabrielle; Paratz, Jennifer D; Thomas, Peter

    2017-06-26

    To describe the processes of care for secretion clearance in adult, intubated and mechanically ventilated patients in Australian and New Zealand Intensive Care Units (ICUs). A prospective, cross-sectional study was conducted through the Australian and New Zealand Intensive Care Society Clinical Trials Group (ANZICS CTG) Point Prevalence Program. Forty-seven ICUs collected data from 230 patients intubated and ventilated on the study day. Secretion clearance techniques beyond standard suctioning were used in 84/230 (37%) of patients during the study period. Chest wall vibration 34/84 (40%), manual lung hyperinflation 24/84 (29%), chest wall percussion 20/84 (24%), postural drainage/patient positioning 17/84 (20%) and other techniques including mobilisation 15/84 (18%), were the most common secretion clearance techniques employed. On average (SD), patients received airway suctioning 8.8 (5.0) times during the 24-h study period. Mucus plugging events were infrequent (2.7%). The additional secretion clearance techniques were provided by physiotherapy staff in 24/47 (51%) ICUs and by both nursing and physiotherapy staff in the remaining 23/47 (49%) ICUs. One-third of intubated and ventilated patients received additional secretion clearance techniques. Mucus plugging events were infrequent with these additional secretion clearance approaches. Prospective studies must examine additional secretion clearance practices, prevalence of mucus plugging episodes and impact on patient outcomes. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  8. Lung clearance of /sup 99m/Tc-DTPA in patients with acute lung injury and pulmonary edema

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Coates, G.; O'Brodovich, H.; Dolovich, M.

    1988-07-01

    Several acute and chronic conditions that alter the integrity of the pulmonary epithelium increased the rate of absorption or clearance into the circulation of small solutes deposited in the alveoli. Technetium 99m diethylenetriamine pentaacetic acid can be deposited in the lungs as a submicronic aerosol and its rate of clearance measured with a gamma camera or simple probe. This clearance technique is currently being used to evaluate patients who have developed pulmonary edema and also to detect those patients from a high risk group who are likely to develop adult respiratory distress syndrome (ARDS). Its role in the evaluation ofmore » patients with pulmonary edema is still under active investigation. It is clear that a single measurement in patients who smoke is not useful, but repeated measurements may provide important information. The lung clearance measurement is very sensitive to changes in epithelial integrity but is not specific for ARDS. It may be most useful in combination with other predictive tests or when the clearance rate is normal. 54 references.« less

  9. Pharmacoepidemiologic investigation of a clonazepam-valproic acid interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.

    PubMed

    Yukawa, E; Nonaka, T; Yukawa, M; Higuchi, S; Kuroda, T; Goto, Y

    2003-12-01

    Non-linear Mixed Effects Modeling (NONMEM) was used to estimate the effects of clonazepam-valproic acid interaction on clearance values using 576 serum levels collected from 317 pediatric and adult epileptic patients (age range, 0.3-32.6 years) during their clinical routine care. Patients received the administration of clonazepam and/or valproic acid. The final model describing clonazepam clearance was CL = 144.0 TBW-0.172 1.14VPA, where CL is total body clearance (mL/kg/h); TBW is total body weight (kg); VPA = 1 for concomitant administration of valproic acid and VPA = zero otherwise. The final model describing valproic acid clearance was CL (mL/kg/h) = 17.2 TBW-0.264 DOSE0.159 0.821CZP 0.896GEN, where DOSE is the daily dose of valproic acid (mg/kg/day); CZP = 1 for concomitant administration of clonazepam and CZP = zero otherwise; GEN = 1 for female and GEN = zero otherwise. Concomitant administration of clonazepam and valproic acid resulted in a 14% increase in clonazepam clearance, and a 17.9% decrease in valproic acid clearance.

  10. Impairment of chemical clearance and mucosal integrity distinguishes hypersensitive esophagus from functional heartburn.

    PubMed

    Frazzoni, Marzio; de Bortoli, Nicola; Frazzoni, Leonardo; Furnari, Manuele; Martinucci, Irene; Tolone, Salvatore; Farioli, Andrea; Marchi, Santino; Fuccio, Lorenzo; Savarino, Vincenzo; Savarino, Edoardo

    2017-04-01

    Hypersensitive esophagus (HE) is defined by endoscopy-negative heartburn with a normal acid exposure time but positive symptom association probability (SAP) and/or symptom index (SI) on impedance-pH monitoring, and proton pump inhibitor (PPI) responsiveness. Functional heartburn (FH) is distinguished by negative SAP/SI and PPI refractoriness. The clinical value of SAP and SI has been questioned. We aimed to investigate whether impairment of chemical clearance and of mucosal integrity, expressed by the postreflux swallow-induced peristaltic wave (PSPW) index and the mean nocturnal baseline impedance (MNBI), characterize HE independently of SAP and SI. Impedance-pH tracings from PPI-responsive endoscopy-negative patients, 125 with nonerosive reflux disease and 108 with HE, distinguished by an abnormal and a normal acid exposure time, and from 70 patients with FH were retrospectively selected and blindly reviewed. The mean PSPW index and MNBI were significantly lower in nonerosive reflux disease (30 %, 1378 Ω) than in HE (51 %; 2274 Ω) and in both of them as compared with FH (76 %; 3445 Ω) (P = 0.0001). Both the PSPW index (adjusted odds ratio 0.863, P = 0.001) and the MNBI (adjusted odds ratio 0.998, P = 0.001) were independent predictors of HE; with their combined assessment, the area under the curve on receiver operating characteristic analysis was 0.957. SAP and/or SI was positive in 67 of the 108 HE patients (62 %), whereas the PSPW index and/or MNBI was abnormal in 99 of the 108 HE patients (92 %; P < 0.0001). HE is characterized by impairment of chemical clearance and mucosal integrity, which explains the increased reflux perception. When SAP and SI afford uncertain results, the PSPW index and MNBI should be analyzed.

  11. Alcohol consumption decreases lactate clearance in acutely injured patients☆

    PubMed Central

    Dezman, Zachary D.W.; Comer, Angela C.; Narayan, Mayur; Scalea, Thomas M.; Hirshon, Jon Mark; Smith, Gordon S.

    2017-01-01

    Introduction Alcohol, a common risk factor for injury, has direct toxic effects on the liver. The use of lactate clearance has been well described as an indicator of the adequacy of resuscitation in injured patients. We investigated whether acutely injured patients with positive blood alcohol content (+BAC) had less lactate clearance than sober patients. Methods We conducted a retrospective cohort study of acutely injured patients treated at an urban Level 1 trauma centre between January 2010 and December 2012. Blood alcohol and venous lactate levels were measured on all patients at the time of arrival. Study subjects were patients transported directly from the scene of injury, who had an elevated lactate concentration on arrival (≥3.0 mmol/L) and at least one subsequent lactate measurement within 24 h after admission. Lactate clearance ([Lactate1 − Lactate2]/Lactate1) was calculated for all patients. Chi-squared tests were used to compare values from sober and intoxicated subjects. Lactate clearance was plotted against alcohol levels and stratified by age and Injury Severity Score (ISS). Results Serial lactate concentration measurements were obtained in 3910 patients; 1674 of them had +BAC. Patients with +BAC were younger (mean age: 36.6 [SD 14.7] vs 41.0 [SD 19.9] years [p = 0.0001]), were more often male (83.4% vs 75.9% [p = 0.0001]), had more minor injuries (ISS < 9) (33.8% vs 27.1% [p = 0.0001]), had a lower in-hospital mortality rate (1.4% vs 3.9% [p = 0.0001]), but also had lower average lactate clearance (37.8% vs 47.6% [p = 0.0001]). The lactate clearance of the sober patients (47.6 [SD 33.5]) was twice that of those with +BAC >400 (23.5 [SD 6.5]). Lactate clearance decreased with increasing BAC irrespective of age and ISS. Conclusions In a large group of acutely injured patients, a dose-dependent decrease in lactate clearance was seen in those with elevated BAC. This relationship will cause a falsely elevated lactate reading or prolong lactate

  12. Duration and clearance of anal human papillomavirus (HPV) infection among women: the Hawaii HPV cohort study.

    PubMed

    Shvetsov, Yurii B; Hernandez, Brenda Y; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Ning, Lily; Killeen, Jeffrey; Kamemoto, Lori; Goodman, Marc T

    2009-03-01

    The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.

  13. Plasma clearance of neostigmine and pyridostigmine in the dog.

    PubMed Central

    Baker, P R; Calvey, T N; Chan, K; Macnee, C M; Taylor, K

    1978-01-01

    1 The pharmacokinetics of neostigmine and pyridostigmine was studied in conscious dogs by the use of a cross-over design. 2 Both neostigmine and pyridostigmine were cleared from plasma in a biexponential manner. 3 The apparent volume of distribution of pyridostigmine was invariably greater than that of neostigmine, and its fast disposition half-life was approximately three times longer. 4 The whole body clearance and the urinary elimination of pyridostigmine was approximately twice that of neostigmine. 5 The slow disposition half-life of pyridostigmine was approximately three times longer than that of neostigmine, suggesting that the longer duration of action of pyridostigmine is related to the differential clearance of the two quarternary amines from plasma. PMID:667495

  14. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance (0.001 in. error).

  15. Evaluation of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Lattime, Scott B.; Taylor, Shawn; DeCastro, Jonathan A.; Oswald, Jay; Melcher, Kevin J.

    2005-01-01

    Reducing blade tip clearances through active tip clearance control in the high pressure turbine can lead to significant reductions in emissions and specific fuel consumption as well as dramatic improvements in operating efficiency and increased service life. Current engines employ scheduled cooling of the outer case flanges to reduce high pressure turbine tip clearances during cruise conditions. These systems have relatively slow response and do not use clearance measurement, thereby forcing cold build clearances to set the minimum clearances at extreme operating conditions (e.g., takeoff, reburst) and not allowing cruise clearances to be minimized due to the possibility of throttle transients (e.g., step change in altitude). In an effort to improve upon current thermal methods, a first generation mechanically-actuated active clearance control (ACC) system has been designed and fabricated. The system utilizes independent actuators, a segmented shroud structure, and clearance measurement feedback to provide fast and precise active clearance control throughout engine operation. Ambient temperature performance tests of this first generation ACC system assessed individual seal component leakage rates and both static and dynamic overall system leakage rates. The ability of the nine electric stepper motors to control the position of the seal carriers in both open- and closed-loop control modes for single and multiple cycles was investigated. The ability of the system to follow simulated engine clearance transients in closed-loop mode showed the system was able to track clearances to within a tight tolerance ( 0.001 in. error).

  16. Accuracy and reproducibility of a new contrast clearance method for the determination of glomerular filtration rate.

    PubMed Central

    O'Reilly, P H; Brooman, P J; Martin, P J; Pollard, A J; Farah, N B; Mason, G C

    1986-01-01

    A new method for determining the glomerular filtration rate was analysed prospectively. The method uses an x ray fluorescence technique to measure disappearance from the plasma of injected non-ionic iodinated contrast media. Eighty seven patients were studied. Fifty four had an intravenous dose of 100 ml iohexol (Omnipaque) and 33 had 50 ml iohexol. Clearances of chromium-51 labelled edetic acid (51Cr-EDTA) were measured simultaneously. In the patients given 100 ml iohexol there was excellent correlation with 51Cr-EDTA clearance (r = 0.90). The correlation using 50 ml iohexol was also good (r = 0.85). Correlation between creatinine clearance and clearance of 51Cr-EDTA in 33 patients was less satisfactory (r = 0.69). There were no adverse reactions to the contrast media. The equipment used for measuring contrast clearance was robust and simple to operate. Freezing plasma samples in 10 studies and re-examining them weekly for six weeks showed no significant variation in results; hence reproducibility was good. This new and accurate method for determining the glomerular filtration rate merits further study and might find a useful place in routine clinical practice. Images FIG 1 PMID:3089467

  17. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance officer...

  18. 48 CFR 945.603-70 - Plant clearance function.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Plant clearance function... Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the contracting officer shall assume all responsibilities of the plant clearance officer...

  19. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket...

  20. 48 CFR 801.602-76 - Business clearance review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is a... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket...

  1. Acute Mucociliary Clearance Response to Aerobic Exercise in Smokers.

    PubMed

    Ramos, Ercy M C; Vanderlei, Luiz Carlos M; Ito, Juliana T; Lima, Fabiano F; Rodrigues, Fernanda M M; Manzano, Beatriz M; Fernandes, Rômulo A; Cecílio, Michel J; Toledo-Arruda, Alessandra C; Ramos, Dionei

    2015-11-01

    Mucociliary clearance is the main defense mechanism of the respiratory system, and it is influenced by several stimuli, including aerobic exercise and cigarette smoking. We evaluated the acute response of mucociliary clearance to aerobic exercise in smokers and nonsmokers compared with that found after acute smoking and smoking combined with exercise. Also, we investigated whether there was a correlation between mucociliary clearance and the autonomic nervous system under these conditions. Twenty-one smokers were evaluated for mucociliary clearance by saccharin transit time (STT), and the response of the autonomic nervous system was evaluated by heart rate variability after aerobic exercise, after exercise followed by smoking, after acute smoking, and after rest. For comparison, 17 nonsmokers were also assessed during exercise. Repeated-measures analysis of variance with the Tukey test or the Friedman test followed by the Dunn test was used to evaluate the STT, autonomic response, and other variables to exercise and/or smoking in smokers. A paired t test or Wilcoxon test was used to analyze responses to exercise in nonsmokers. Correlations were evaluated using Pearson or Spearman coefficients. The STT was reduced after exercise in both groups, with similar responses between them. Other stimuli also reduced the STT. The STT showed a negative correlation with sympathetic activity in smokers and a positive correlation with the parasympathetic system in nonsmokers. Although impaired in smokers, mucociliary clearance responded to the stimulus of exercise, as demonstrated by similar STTs compared with nonsmokers. This response was correlated with the autonomic nervous system in both groups. In smokers, mucociliary clearance also responded to the stimuli of smoking and exercise followed by smoking. Copyright © 2015 by Daedalus Enterprises.

  2. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor surfaces, or between uninsulated conductor surfaces and grounded metal surfaces, within the enclosure shall...

  3. 30 CFR 18.24 - Electrical clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical conductor surfaces, or between uninsulated conductor surfaces and grounded metal surfaces, within the enclosure shall...

  4. Accuracy of indocyanine green pulse spectrophotometry clearance test for liver function prediction in transplanted patients

    PubMed Central

    Hsieh, Chung-Bao; Chen, Chung-Jueng; Chen, Teng-Wei; Yu, Jyh-Cherng; Shen, Kuo-Liang; Chang, Tzu-Ming; Liu, Yao-Chi

    2004-01-01

    AIM: To investigate whether the non-invasive real-time Indocynine green (ICG) clearance is a sensitive index of liver viability in patients before, during, and after liver transplantation. METHODS: Thirteen patients were studied, two before, three during, and eight following liver transplantation, with two patients suffering acute rejection. The conventional invasive ICG clearance test and ICG pulse spectrophotometry non-invasive real-time ICG clearance test were performed simultaneously. Using linear regression analysis we tested the correlation between these two methods. The transplantation condition of these patients and serum total bilirubin (T. Bil), alanine aminotransferase (ALT), and platelet count were also evaluated. RESULTS: The correlation between these two methods was excellent (r2 = 0.977). CONCLUSION: ICG pulse spectrophotometry clearance is a quick, non-invasive, and reliable liver function test in transplantation patients. PMID:15285026

  5. 45 CFR 675.3 - Medical clearance criteria.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Medical clearance criteria. 675.3 Section 675.3 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION MEDICAL CLEARANCE PROCESS FOR DEPLOYMENT TO ANTARCTICA § 675.3 Medical clearance criteria. (a) The USAP shall...

  6. 45 CFR 675.3 - Medical clearance criteria.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Medical clearance criteria. 675.3 Section 675.3 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION MEDICAL CLEARANCE PROCESS FOR DEPLOYMENT TO ANTARCTICA § 675.3 Medical clearance criteria. (a) The USAP shall...

  7. 45 CFR 675.3 - Medical clearance criteria.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Medical clearance criteria. 675.3 Section 675.3 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION MEDICAL CLEARANCE PROCESS FOR DEPLOYMENT TO ANTARCTICA § 675.3 Medical clearance criteria. (a) The USAP shall...

  8. P301L tau expression affects glutamate release and clearance in the hippocampal trisynaptic pathway.

    PubMed

    Hunsberger, Holly C; Rudy, Carolyn C; Batten, Seth R; Gerhardt, Greg A; Reed, Miranda N

    2015-01-01

    Individuals at risk of developing Alzheimer's disease (AD) often exhibit hippocampal hyperexcitability. A growing body of evidence suggests that perturbations in the glutamatergic tripartite synapse may underlie this hyperexcitability. Here, we used a tau mouse model of AD (rTg(TauP301L)4510) to examine the effects of tau pathology on hippocampal glutamate regulation. We found a 40% increase in hippocampal vesicular glutamate transporter, which packages glutamate into vesicles, and has previously been shown to influence glutamate release, and a 40% decrease in hippocampal glutamate transporter 1, the major glutamate transporter responsible for removing glutamate from the extracellular space. To determine whether these alterations affected glutamate regulation in vivo, we measured tonic glutamate levels, potassium-evoked glutamate release, and glutamate uptake/clearance in the dentate gyrus, cornu ammonis 3(CA3), and cornu ammonis 1(CA1) regions of the hippocampus. P301L tau expression resulted in a 4- and 7-fold increase in potassium-evoked glutamate release in the dentate gyrus and CA3, respectively, and significantly decreased glutamate clearance in all three regions. Both release and clearance correlated with memory performance in the hippocampal-dependent Barnes maze task. Alterations in mice expressing P301L were observed at a time when tau pathology was subtle and before readily detectable neuron loss. These data suggest novel mechanisms by which tau may mediate hyperexcitability. Pre-synaptic vesicular glutamate transporters (vGLUTs) package glutamate into vesicles before exocytosis into the synaptic cleft. Once in the extracellular space, glutamate acts on glutamate receptors. Glutamate is removed from the extracellular space by excitatory amino acid transporters, including GLT-1, predominantly localized to glia. P301L tau expression increases vGLUT expression and glutamate release, while also decreasing GLT-1 expression and glutamate clearance. © 2014

  9. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

  10. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

  11. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

  12. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

  13. 24 CFR 3285.305 - Clearance under homes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Clearance under homes. 3285.305... URBAN DEVELOPMENT MODEL MANUFACTURED HOME INSTALLATION STANDARDS Foundations § 3285.305 Clearance under homes. A minimum clearance of 12 inches must be maintained between the lowest member of the main frame...

  14. Lactic acid peeling in superficial acne scarring in Indian skin.

    PubMed

    Sachdeva, Silonie

    2010-09-01

    Chemical peeling with both alpha and beta hydroxy acids has been used to improve acne scarring with pigmentation. Lactic acid, a mild alpha hydroxy acid, has been used in the treatment of various dermatological indications but no study is reported in acne scarring with pigmentation. To evaluate the efficacy and safety of full strength pure lactic acid 92% (pH 2.0) chemical peel in superficial acne scarring in Indian skin. Seven patients, Fitzpatrick skin type IV-V, in age group 20-30 years with superficial acne scarring were enrolled in the study. Chemical peeling was done with lactic acid at an interval of 2 weeks to a maximum of four peels. Pre- and post-peel clinical photographs were taken at every session. Patients were followed every month for 3 months after the last peel to evaluate the effects. At the end of 3 months, there was definite improvement in the texture, pigmentation, and appearance of the treated skin, with lightening of scars. Significant improvement (greater than 75% clearance of lesions) occurred in one patient (14.28%), good improvement (51-75% clearance) in three patients (42.84%), moderate improvement (26-50% clearance) in two patients (28.57%), and mild improvement (1-25% clearance) in one patient (14.28%). © 2010 Wiley Periodicals, Inc.

  15. 46 CFR 56.75-10 - Joint clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Joint clearance. 56.75-10 Section 56.75-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PIPING SYSTEMS AND APPURTENANCES Brazing § 56.75-10 Joint clearance. (a) The clearance between surfaces to be joined shall be no...

  16. Compressor airfoil tip clearance optimization system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Little, David A.; Pu, Zhengxiang

    2015-08-18

    A compressor airfoil tip clearance optimization system for reducing a gap between a tip of a compressor airfoil and a radially adjacent component of a turbine engine is disclosed. The turbine engine may include ID and OD flowpath boundaries configured to minimize compressor airfoil tip clearances during turbine engine operation in cooperation with one or more clearance reduction systems that are configured to move the rotor assembly axially to reduce tip clearance. The configurations of the ID and OD flowpath boundaries enhance the effectiveness of the axial movement of the rotor assembly, which includes movement of the ID flowpath boundary.more » During operation of the turbine engine, the rotor assembly may be moved axially to increase the efficiency of the turbine engine.« less

  17. Effects of Esophageal Acidification on Troublesome Symptoms: An Approach to Characterize True Acid GERD in Dysphagic Neonates.

    PubMed

    Sivalingam, Maneesha; Sitaram, Swetha; Hasenstab, Kathryn A; Wei, Lai; Woodley, Frederick W; Jadcherla, Sudarshan R

    2017-08-01

    To quantify and compare maximal extent (height) of acid reflux events (AREs) on symptom generation in dysphagic neonates. Dysphagic neonates (N = 53), born at 30 ± 5.3 weeks gestation, underwent 24-hour pH-impedance study for the evaluation of troublesome symptoms purported to be due to gastroesophageal reflux disease (GERD). AREs (pH < 4 for >4 s) detected by impedance (Z) were categorized by maximal extent as refluxate reaching distal (Z6, Z5), middle (Z4, Z3), or proximal (Z2, Z1) impedance channels. AREs reaching the pH sensor only were categorized as distal. Symptom correlation (%, symptom index, symptom sensitivity index, and symptom associated probability) and temporal characteristics (clearance times) of AREs were analyzed using linear mixed and GEE models comparing height categories presented as mean ± SEM, median (IQR), and OR (95% CI). Of the 2003 AREs, 1) distal extent AREs (n = 1642) had increased frequency (p < 0.05), decreased ACT (p < 0.05), and decreased acidity (p < 0.05); 2) in middle and proximal AREs, acid clearance was longer than bolus clearance, (p < 0.01); and 3) the odds of having cardiorespiratory (cough or sneeze) symptoms are increased with proximal and middle AREs (p < 0.05). Most proximal ascent of AREs into middle or proximal esophagus likely activates protective aerodigestive reflexes (peristalsis) or vigilant states to facilitate bolus and chemical clearance. Heightened esophageal sensitivity, acid neutralization delays, or clearance mechanism delays may accentuate multi-systemic troublesome symptoms.

  18. TAM receptors in apoptotic cell clearance, autoimmunity, and cancer.

    PubMed

    Nguyen, Khanh-Quynh; Tsou, Wen-I; Kotenko, Sergei; Birge, Raymond B

    2013-08-01

    Receptor tyrosine kinases, Tyro-3, Axl and Mer, collectively designated as TAM, are involved in the clearance of apoptotic cells. TAM ligands, Gas6 and Protein S, bind to the surfaces of apoptotic cells, and at the same time, interact directly with TAM expressed on phagocytes, impacting the engulfment and clearance of apoptotic cells and debris. The well-tuned and balanced actions of TAM may affect a variety of human pathologies including autoimmunity, retinal degeneration, and cancer. This article emphasizes some of the emerging findings and mechanistic insights into TAM functions that are clinically relevant and possibly therapeutically targeted.

  19. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance

    NASA Astrophysics Data System (ADS)

    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R. James; Whelan, Eoin C.; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-01

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 109 M-1 cm-1 and 1.5 × 108 M-1 cm-1 respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

  20. Low-coherence interferometric tip-clearance probe

    NASA Astrophysics Data System (ADS)

    Kempe, Andreas; Schlamp, Stefan; Rösgen, Thomas; Haffner, Ken

    2003-08-01

    We propose an all-fiber, self-calibrating, economical probe that is capable of near-real-time, single-port, simultaneous blade-to-blade tip-clearance measurements with submillimeter accuracy (typically <100 μm, absolute) in the first stages of a gas turbine. Our probe relies on the interference between backreflected light from the blade tips during the 1-μs blade passage time and a frequency-shifted reference with variable time delay, making use of a low-coherence light source. A single optical fiber of arbitrary length connects the self-contained optics and electronics to the turbine.

  1. Development of a Novel System to Measure a Clearance of a Passenger Platform

    NASA Astrophysics Data System (ADS)

    Shimizu, M.; Oizumi, J.; Matsuoka, R.; Takeda, H.; Okukura, H.; Ooya, A.; Koike, A.

    2016-06-01

    Clearances of a passenger platform at a railway station should be appropriately maintained for safety of both trains and passengers. In most Japanese railways clearances between a platform and a train car is measured precisely once or twice a year. Because current measurement systems operate on a track, the closure of the track is unavoidable. Since the procedure of the closure of a track is time-consuming and bothersome, we decided to develop a new system to measure clearances without the closure of a track. A new system is required to work on a platform and the required measurement accuracy is less than several millimetres. We have adopted a 3D laser scanner and stop-and-go operation for a new system. The current systems on a track measure clearances continuously at walking speed, while our system on a platform measures clearances at approximately ten metres intervals. The scanner controlled by a PC acquires a set of point data at each measuring station. Edge points of the platform, top and side points of two rails are detected from the acquired point data. Finally clearances of the platform are calculated by using the detected feature points of the platform and the rails. The results of an experiment using a prototype of our system show that the measurement accuracy by our system would be satisfactory, but our system would take more time than the current systems. Since our system requires no closure of a track, we conclude that our system would be convenient and effective.

  2. A model of clearance rate regulation in mussels

    NASA Astrophysics Data System (ADS)

    Fréchette, Marcel

    2012-10-01

    Clearance rate regulation has been modelled as an instantaneous response to food availability, independent of the internal state of the animals. This view is incompatible with latent effects during ontogeny and phenotypic flexibility in clearance rate. Internal-state regulation of clearance rate is required to account for these patterns. Here I develop a model of internal-state based regulation of clearance rate. External factors such as suspended sediments are included in the model. To assess the relative merits of instantaneous regulation and internal-state regulation, I modelled blue mussel clearance rate and growth using a DEB model. In the usual standard feeding module, feeding is governed by a Holling's Type II response to food concentration. In the internal-state feeding module, gill ciliary activity and thus clearance rate are driven by internal reserve level. Factors such as suspended sediments were not included in the simulations. The two feeding modules were compared on the basis of their ability to capture the impact of latent effects, of environmental heterogeneity in food abundance and of physiological flexibility on clearance rate and individual growth. The Holling feeding module was unable to capture the effect of any of these sources of variability. In contrast, the internal-state feeding module did so without any modification or ad hoc calibration. Latent effects, however, appeared transient. With simple annual variability in temperature and food concentration, the relationship between clearance rate and food availability predicted by the internal-state feeding module was quite similar to that observed in Norwegian fjords. I conclude that in contrast with the usual Holling feeding module, internal-state regulation of clearance rate is consistent with well-documented growth and clearance rate patterns.

  3. Study of blade clearance effects on centrifugal pumps

    NASA Technical Reports Server (NTRS)

    Hoshide, R. K.; Nielson, C. E.

    1972-01-01

    A program of analysis, design, fabrication, and testing has been conducted to develop and experimentally verify analytical models to predict the effects of impeller blade clearance on centrifugal pumps. The effect of tip clearance on pump efficiency, and the relationship between the head coefficient and torque loss with tip clearance was established. Analysis were performed to determine the cost variation in design, manufacture, and test that would occur between unshrouded and shrouded impellers. An impeller, representative of typical rocket engine impellers, was modified by removing its front shroud to permit variation of its blade clearances. It was tested in water with special instrumentation to provide measurements of blade surface pressures during operation. Pump performance data were obtained from tests at various impeller tip clearances. Blade pressure data were obtained at the nominal tip clearance. Comparisons of predicted and measured data are given.

  4. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

  5. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

  6. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

  7. 48 CFR 245.602-70 - Plant clearance procedures.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Plant clearance procedures... Disposal 245.602-70 Plant clearance procedures. Follow the procedures at PGI 245.602-70 for establishing and processing a plant clearance case. ...

  8. Predicting Human Clearance of OATP substrates using Cynomolgus monkey: In vitro-in vivo scaling of hepatic uptake clearance.

    PubMed

    de Bruyn, Tom; Ufuk, Ayse; Cantrill, Carina; Kosa, Rachel E; Bi, Yi-An; Niosi, Mark; Modi, Sweta; Rodrigues, A David; Tremaine, Larry M; Varma, Manthena Vs; Galetin, Aleksandra; Houston, J Brian

    2018-05-02

    This work explores the utility of the cynomolgus monkey as a preclinical model to predict hepatic uptake clearance mediated by organic anion transporting polypeptide (OATP) transporters. Nine OATP substrates (rosuvastatin, pravastatin, repaglinide, fexofenadine, cerivastatin, telmisartan, pitavastatin, bosentan and valsartan) were investigated in plated cynomolgus monkey and human hepatocytes. Total uptake clearance and passive diffusion were measured in vitro from initial rates in the absence and presence of the OATP inhibitor rifamycin SV, respectively. Total uptake clearance values in plated hepatocytes ranged over three orders of magnitude in both species with a similar rank order and good agreement in the relative contribution of active transport to total uptake between cynomolgus monkey and human. In vivo hepatic clearance for these nine drugs was determined in cynomolgus monkey after intravenous dosing. Hepatic clearances showed a similar range to human parameters and good predictions from respective hepatocyte parameters (with 2.7 and 3.8-fold bias on average, respectively). The use of cross species empirical scaling factors (based on either dataset average or individual drug scaling factor from cynomolgus monkey data) improved prediction (less bias, better concordance) of human hepatic clearance from human hepatocyte data alone. In vitro intracellular binding in hepatocytes also correlated well between species. It is concluded that the minimal species differences observed for the current dataset between cynomolgus monkey and human hepatocyte uptake, both in vitro and in vivo, support future use of this preclinical model to delineate drug hepatic uptake and enable prediction of human in vivo intrinsic hepatic clearance. The American Society for Pharmacology and Experimental Therapeutics.

  9. Simple sampling strategy for measuring inulin renal clearance.

    PubMed

    Horio, Masaru; Imai, Enyu; Yasuda, Yoshinari; Hishida, Akira; Matsuo, Seiichi

    2009-02-01

    In the standard method of inulin clearance (Cin), three sets of serum and urine samples are collected during a 2-hour clearance period. For a practical use of this method, sampling should be the minimal number allowable while still providing enough accuracy. The aim of this study was to evaluate the validity of inulin renal clearance with assumed single urine collection with a period such as 30, 60 or 90 minutes. Inulin clearance data collected by the standard method from 737 individuals were used. Changes of serum inulin concentrations between 45 and 105 minutes after the start of the infusion were analyzed. We used first urine collection to calculate the inulin clearance with single urine collection (Cin-30 min). We assumed single urine collection for 60 or 90 minutes by combining the urine data of the consecutive 30-minute periods. Inulin clearances (Cin-60 min, Cin-90 min) were calculated from the assumed single urine collections, respectively. Serum inulin concentration did not reach equilibrium during the clearance period. It increased in subjects with low glomerular filtration rate (GFR) and decreased in subjects with normal GFR. The amount of the change was small and -0.5 +/- 12.6% in subjects with GFR over 30 ml/min per 1.73 m(2). Cin-30 min, Cin-60 min and Cin-90 min showed high correlation coefficients against Cin-ST (0.962, 0.988 and 0.998, respectively). Systemic biases in these clearances were negligible (under 1 ml/min per 1.73 m(2)). Root mean square error (RMSE) were 10.4, 5.3 and 2.3 ml/min per 1.73 m(2) for Cin-30 min, Cin-60 min and Cin-90 min, respectively. These data indicated that accuracy of inulin clearance depends on the duration of the urine collection period. Inulin clearance with a single urine collection is a convenient method. We showed that single urine collection for 30 minutes or a longer period has reasonable accuracy in calculation of inulin clearance. We propose a method of inulin clearance with single urine collection for 60

  10. 78 FR 77027 - Overhead Clearance (Air-Draft) Accidents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... No. USCG-2013-0466] Overhead Clearance (Air-Draft) Accidents AGENCY: Coast Guard, DHS. ACTION... clearance (air-draft) accidents. In its petition, which calls for vessel masters to be provided with accurate vertical air draft information, a maritime organization has described 16 overhead clearance...

  11. Fault Diagnosis of Internal Combustion Engine Valve Clearance Using the Impact Commencement Detection Method

    PubMed Central

    Jiang, Zhinong; Wang, Zijia; Zhang, Jinjie

    2017-01-01

    Internal combustion engines (ICEs) are widely used in many important fields. The valve train clearance of an ICE usually exceeds the normal value due to wear or faulty adjustment. This work aims at diagnosing the valve clearance fault based on the vibration signals measured on the engine cylinder heads. The non-stationarity of the ICE operating condition makes it difficult to obtain the nominal baseline, which is always an awkward problem for fault diagnosis. This paper overcomes the problem by inspecting the timing of valve closing impacts, of which the referenced baseline can be obtained by referencing design parameters rather than extraction during healthy conditions. To accurately detect the timing of valve closing impact from vibration signals, we carry out a new method to detect and extract the commencement of the impacts. The results of experiments conducted on a twelve-cylinder ICE test rig show that the approach is capable of extracting the commencement of valve closing impact accurately and using only one feature can give a superior monitoring of valve clearance. With the help of this technique, the valve clearance fault becomes detectable even without the comparison to the baseline, and the changing trend of the clearance could be trackable. PMID:29244722

  12. Fault Diagnosis of Internal Combustion Engine Valve Clearance Using the Impact Commencement Detection Method.

    PubMed

    Jiang, Zhinong; Mao, Zhiwei; Wang, Zijia; Zhang, Jinjie

    2017-12-15

    Internal combustion engines (ICEs) are widely used in many important fields. The valve train clearance of an ICE usually exceeds the normal value due to wear or faulty adjustment. This work aims at diagnosing the valve clearance fault based on the vibration signals measured on the engine cylinder heads. The non-stationarity of the ICE operating condition makes it difficult to obtain the nominal baseline, which is always an awkward problem for fault diagnosis. This paper overcomes the problem by inspecting the timing of valve closing impacts, of which the referenced baseline can be obtained by referencing design parameters rather than extraction during healthy conditions. To accurately detect the timing of valve closing impact from vibration signals, we carry out a new method to detect and extract the commencement of the impacts. The results of experiments conducted on a twelve-cylinder ICE test rig show that the approach is capable of extracting the commencement of valve closing impact accurately and using only one feature can give a superior monitoring of valve clearance. With the help of this technique, the valve clearance fault becomes detectable even without the comparison to the baseline, and the changing trend of the clearance could be trackable.

  13. Confusion in Using Pre-Departure Clearances

    DOT National Transportation Integrated Search

    1996-12-20

    In 1990, the FAA implemented the Pre-Departure Clearance (PDC) program at a : number of U.S. airports. This system allows pilots to obtain IFR clearances : through aircraft ACARS units prior to taxi-out, thus eliminating the need for : verbal communi...

  14. Shape memory alloy adaptive control of gas turbine engine compressor blade tip clearance

    NASA Astrophysics Data System (ADS)

    Schetky, Lawrence M.; Steinetz, Bruce M.

    1998-06-01

    The ambient air ingested through the inlet of a gas turbine is first compressed by an axial compressor followed by further compression in a centrifugal compressor and then fed into the combustion chamber where ignition and expansion take place to produce the engine thrust. The axial compressor typically has five or more stages which consist of revolving blades and stators and the overall performance of the turbine is strongly affected by the compressor efficiency. When the turbine is turned on, to accommodate the rapid initial increase in the compressor blade length due to centrifugal force, the cold turbine has a built in clearance between the turbine blade tip and the casing. As the turbine reached its operating temperature there is a further increase in the blade length due to thermal expansion and, at the same time, the diameter of the casing increases. The net result is that when these various components have reached their equilibrium temperatures, the initial cold build clearance is reduced, but there remains a residual clearance. The magnitude of this clearance has a direct effect on the compressor efficiency and can be stated as: Δη/Δ CLR equals 0.5 where η is efficiency and CLR is the tip clearance. The concept of adaptive tip clearance control is based on the ability of a shape memory alloy ring to shrink to a predetermined diameter when heated to the temperature of a particular stage, and thus reducing the tip clearance. The ring is fabricated from a CuAlNi shape memory alloy and is mounted in the casing so as to be coaxial with the rotating blades of the particular stage. When cold, the ring dimensions are such as to provide the required cold build clearance, but when at operating temperature the reduced diameter creates a very small tip clearance. The clearance provided by this concept is much smaller than the clearance normally obtained for a turbine of the size being studied.

  15. Aerial Refueling Clearance Initiation Request

    DTIC Science & Technology

    2016-07-14

    and receiver agencies. The AR Clearance Initiation Request document recognizes the requirement for definitive aerial refueling agreements between...and contractual tanker support requests from one organization or nation to another. The AR Clearance Initiation Request document is not intended to...proprietary, sensitive, classified or otherwise restricted information. ARSAG documents, as prepared, are not DOD, MOD or NATO standards, but provide

  16. Lack of effect of non-steroid antiinflammatory drugs on lithium clearance and on delivery of tubular fluid to the loop of Henle in rats.

    PubMed

    Lassen, E; Thomsen, K; Sørensen, S S; Pedersen, E B

    1986-11-01

    This paper examines a possible interaction between non-steroid antiinflammatory drugs (NSAI drugs) and renal lithium clearance in conscious, unoperated rats with diabetes insipidus (Brattleboro strain) and ordinary Wistar rats. The drugs were given with the food for 5 days before clearance determinations in the following daily doses per kg body weight: acetylsalicyclic acid 115 mg/kg, phenylbutazone 20 mg/kg, indomethacin 5 mg/kg, and penicillamine 65 mg/kg. None of the drugs affected the lithium clearance. Also urine flow, sodium clearance, potassium clearance, and prostaglandin E2 excretion remained unaffected by the treatments. The results suggest that a continued lowering of lithium clearance cannot be produced, at least not by administration of the drugs with the food. Since lithium clearance is a quantitative measure of the delivery of tubular fluid from the proximal tubules to the loop of Henle, the results also suggest that chronic administration of NSAI drugs does not influence delivery from the proximal tubules in rats. The lowering of lithium clearance observed by others after administration of the drugs by injection or by gastric tube may have been transient, lasting only for a short period after each administration.

  17. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the...

  18. 48 CFR 945.670-1 - Plant clearance function.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Plant clearance function... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 945.670-1 Plant clearance function. If the plant clearance function has not been formally delegated to another Federal agency, the...

  19. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air-sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. Each abatement took place in a school buildi...

  20. AHERA CLEARANCE AT TWENTY ABATEMENT SITES

    EPA Science Inventory

    A study was conducted during the summer of 1988 to document Asbestos Hazard Emergency Response Act (AHERA) clearance air sampling practices and clearance concentrations of airborne asbestos at 20 asbestos-abatement sites in New Jersey. ach abatement took place in a school buildin...

  1. Shear joint capability versus bolt clearance

    NASA Technical Reports Server (NTRS)

    Lee, H. M.

    1992-01-01

    The results of a conservative analysis approach into the determination of shear joint strength capability for typical space-flight hardware as a function of the bolt-hole clearance specified in the design are presented. These joints are comprised of high-strength steel fasteners and abutments constructed of aluminum alloys familiar to the aerospace industry. A general analytical expression was first arrived at which relates bolt-hole clearance to the bolt shear load required to place all joint fasteners into a shear transferring position. Extension of this work allowed the analytical development of joint load capability as a function of the number of fasteners, shear strength of the bolt, bolt-hole clearance, and the desired factor of safety. Analysis results clearly indicate that a typical space-flight hardware joint can withstand significant loading when less than ideal bolt hole clearances are used in the design.

  2. Fuel conservation through active control of rotor clearances

    NASA Technical Reports Server (NTRS)

    Beitler, R. S.; Saunders, A. A.; Wanger, R. P.

    1980-01-01

    Under the NASA-sponsored Energy Efficient Engine (EEE) Project, technology is being developed which will significantly reduce the fuel consumption of turbofan engines for subsonic transport aircraft. One technology concept being pursued is active control of rotor tip clearances. Attention is given to rotor tip clearance considerations and an overview of preliminary study results as well as the General Electric EEE clearance control approach is presented. Finally, potential fuel savings with active control of rotor clearances for a typical EEE mission are predicted.

  3. Predictive factors of spontaneous CMV DNAemia clearance in kidney transplantation.

    PubMed

    Noble, Johan; Gatault, Philippe; Sautenet, Bénédicte; Gaudy-Graffin, Catherine; Beby-Defaux, Agnes; Thierry, Antoine; Essig, Marie; Halimi, Jean-Michel; Munteanu, Eliza; Alain, Sophie; Buchler, Matthias

    Cytomegalovirus (CMV) infection occurs frequently after solid organ transplantation. Therapeutic strategies, in particular when to start a curative treatment, has not yet been defined. The purpose of this study was to assess predictive factors associated with spontaneous clearance of CMV DNAemia in kidney transplant recipients. All kidney recipients of a single center were recruited. Patients with at least one positive CMV DNAemia during the first year post transplantation were included in our analysis. Whole blood CMV PCR was performed using Abbott ® RealTime CMV, calibrated according to WHO standards and expressed in log10 IU/ml (Detection = 1.79 IU log10/ml). Post transplantation, prophylaxis (valganciclovir) was given for 3 months for CMV positive recipients (R+) and 6 months for CMV positive donors giving to seronegative recipients (D + R-). Clinical and biological symptoms attributable to CMV were collected. We defined as spontaneous CMV clearance undetectable DNAemia before the fourth follow up without treatment. Results were expressed as mean ± SD. Results were prospectively assessed in a French multicenter validation cohort. Between 05/2012 and 05/2015, 95 patients had at least one positive CMV DNAemia. Thirty-six (37.8%) had spontaneous undetectable DNAemia. Fifty-nine patients had non-spontaneous CMV clearance. ROC analysis showed that an initial CMV DNAemia <2.75 log10/IU/mL was optimal to predict CMV spontaneous clearance. On multivariate analysis, factors associated with spontaneous CMV clearance were initial PCR level lower than 2.75 log10/IU/ml (OR = 33.8, 95% CI [7.1-160.0]), and absence of CMV DNAemia increase of more than 1 log10 between two analyses (OR = 128.0, 95% CI [11.9-1368.0]). Clinical and biological abnormalities were not associated CMV DNAemia spontaneous clearance. Observations made for the principal cohort were validated in an independent cohort of 49 kidney transplanted patients. Initial standardized

  4. Analysis of middle bearing failure in rotor jet engine using tip-timing and tip-clearance techniques

    NASA Astrophysics Data System (ADS)

    Rzadkowski, R.; Rokicki, E.; Piechowski, L.; Szczepanik, R.

    2016-08-01

    The reported problem is the failure of the middle bearing in an aircraft rotor engine. Tip-timing and tip-clearance and variance analyses are carried out on a compressor rotor blade in the seventh stage above the middle bearing. The experimental analyses concern both an aircraft engine with a middle bearing in good working order and an engine with a damaged middle bearing. A numerical analysis of seventh stage blade free vibration is conducted to explain the experimental results. This appears to be an effective method of predicting middle bearing failure. The results show that variance first increases in the initial stages of bearing failure, but then starts to decrease and stabilize, and then again decrease shortly before complete bearing failure.

  5. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Export clearance. 752.15 Section 752... OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL COMPREHENSIVE LICENSE § 752.15 Export clearance. (a) Shipper's Export Declaration (SED) or Automated Export...

  6. ADAPTIVE CLEARANCE CONTROL SYSTEMS FOR TURBINE ENGINES

    NASA Technical Reports Server (NTRS)

    Blackwell, Keith M.

    2004-01-01

    The Controls and Dynamics Technology Branch at NASA Glenn Research Center primarily deals in developing controls, dynamic models, and health management technologies for air and space propulsion systems. During the summer of 2004 I was granted the privilege of working alongside professionals who were developing an active clearance control system for commercial jet engines. Clearance, the gap between the turbine blade tip and the encompassing shroud, increases as a result of wear mechanisms and rubbing of the turbine blades on shroud. Increases in clearance cause larger specific fuel consumption (SFC) and loss of efficient air flow. This occurs because, as clearances increase, the engine must run hotter and bum more fuel to achieve the same thrust. In order to maintain efficiency, reduce fuel bum, and reduce exhaust gas temperature (EGT), the clearance must be accurately controlled to gap sizes no greater than a few hundredths of an inch. To address this problem, NASA Glenn researchers have developed a basic control system with actuators and sensors on each section of the shroud. Instead of having a large uniform metal casing, there would be sections of the shroud with individual sensors attached internally that would move slightly to reform and maintain clearance. The proposed method would ultimately save the airline industry millions of dollars.

  7. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

  8. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

  9. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

  10. 14 CFR 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For...

  11. Defective Autophagy, Mitochondrial Clearance and Lipophagy in Niemann-Pick Type B Lymphocytes

    PubMed Central

    Salucci, Sara; Luchetti, Francesca; Falcieri, Elisabetta; Di Sario, Gianna; Palma, Fulvio; Papa, Stefano

    2016-01-01

    Niemann-Pick disease type A (NP-A) and type B (NP-B) are lysosomal storage diseases (LSDs) caused by sphingomyelin accumulation in lysosomes relying on reduced or absent acid sphingomyelinase. A considerable body of evidence suggests that lysosomal storage in many LSD impairs autophagy, resulting in the accumulation of poly-ubiquitinated proteins and dysfunctional mitochondria, ultimately leading to cell death. Here we test this hypothesis in a cellular model of Niemann-Pick disease type B, in which autophagy has never been studied. The basal autophagic pathway was first examined in order to evaluate its functionality using several autophagy-modulating substances such as rapamycin and nocodazole. We found that human NP-B B lymphocytes display considerable alteration in their autophagic vacuole accumulation and mitochondrial fragmentation, as well as mitophagy induction (for damaged mitochondria clearance). Furthermore, lipid traceability of intra and extra-cellular environments shows lipid accumulation in NP-B B lymphocytes and also reveals their peculiar trafficking/management, culminating in lipid microparticle extrusion (by lysosomal exocytosis mechanisms) or lipophagy. All of these features point to the presence of a deep autophagy/mitophagy alteration revealing autophagic stress and defective mitochondrial clearance. Hence, rapamycin might be used to regulate autophagy/mitophagy (at least in part) and to contribute to the clearance of lysosomal aberrant lipid storage. PMID:27798705

  12. 19 CFR 122.77 - Clearance certificate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart; Electronic...

  13. A novel mouse model for sudden unexpected death in epilepsy (SUDEP): role of impaired adenosine clearance.

    PubMed

    Shen, Hai-Ying; Li, Tianfu; Boison, Detlev

    2010-03-01

    Sudden unexpected death in epilepsy (SUDEP) is a significant cause of mortality in people with epilepsy. Two postulated causes for SUDEP, cardiac and respiratory depression, can both be explained by overstimulation of adenosine receptors. We hypothesized that SUDEP is a consequence of a surge in adenosine as a result of prolonged seizures combined with deficient adenosine clearance; consequently, blockade of adenosine receptors should prevent SUDEP. Here we induced impaired adenosine clearance in adult mice by pharmacologic inhibition of the adenosine-removing enzymes, adenosine kinase and deaminase. Combination of impaired adenosine clearance with kainic acid-induced seizures triggered sudden death in all animals. Most importantly, the adenosine receptor antagonist caffeine, when given after seizure onset, increased survival from 23.75 +/- 1.35 min to 54.86 +/- 6.59 min (p < 0.01). Our data indicate that SUDEP is due to overactivation of adenosine receptors and that caffeine treatment after seizure onset might be beneficial.

  14. Hepatic and muscle clearance of physostigmine in the rat after i. v. administration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Somani, S.M.; Unni, L.K.

    1986-03-01

    This study presents a method to calculate the extraction ratio (ER) from in vivo time course of liver metabolism using the physiological and pharmacokinetic parameters such as plasma flow rate, partition coefficient of drug between tissue and plasma and the elimination rate constant from tissues. Rats were administered /sup 3/H-physostigmine (Phy), 100 ..mu..g/kg i.v.; and were sacrificed at various times. Tissues were removed and Phy and its metabolites were determined by HPLC. Half-life of Phy in liver and muscle was 24 and 20 min, respectively. ER of Phy in liver was .71 which showed a slight decrease at 10 min.more » Muscle ER was found to be .347 up to 5 min. Hepatic clearance was calculated to be 23.08 ml/min/kg (34.9% of systemic clearance) and the intrinsic clearance was 83.73 ml/min/kg which indicates that the changes in blood flow to the liver can cause a variation in the systematic clearance. Percentage dose of Phy retained in muscle was maximum and the clearance was 5.2 ml/min/kg suggesting that muscle might be acting as a storage depot for Phy prolonging the pharmacological effects. About 30-40% of radioactivity in the liver could not be washed off by 10% TCA or organic solvents indicating the irreversible binding of drug or metabolite to liver macromolecule.« less

  15. Integrated Turbine Tip Clearance and Gas Turbine Engine Simulation

    NASA Technical Reports Server (NTRS)

    Chapman, Jeffryes W.; Kratz, Jonathan; Guo, Ten-Huei; Litt, Jonathan

    2016-01-01

    Gas turbine compressor and turbine blade tip clearance (i.e., the radial distance between the blade tip of an axial compressor or turbine and the containment structure) is a major contributing factor to gas path sealing, and can significantly affect engine efficiency and operational temperature. This paper details the creation of a generic but realistic high pressure turbine tip clearance model that may be used to facilitate active tip clearance control system research. This model uses a first principles approach to approximate thermal and mechanical deformations of the turbine system, taking into account the rotor, shroud, and blade tip components. Validation of the tip clearance model shows that the results are realistic and reflect values found in literature. In addition, this model has been integrated with a gas turbine engine simulation, creating a platform to explore engine performance as tip clearance is adjusted. Results from the integrated model explore the effects of tip clearance on engine operation and highlight advantages of tip clearance management.

  16. Effect of a keto acid-amino acid supplement on the metabolism and renal elimination of branched-chain amino acids in patients with chronic renal insufficiency on a low protein diet.

    PubMed

    Teplan, V; Schück, O; Horácková, M; Skibová, J; Holecek, M

    2000-10-27

    The aim of our study was to evaluate the effect of a low-protein diet supplemented with keto acids-amino acids on renal function and urinary excretion of branched-chain amino acids (BCAA) in patients with chronic renal insufficiency (CRI). In a prospective investigation 28 patients with CRI (16 male, 12 female, aged 28-66 yrs, CCr 18.6 +/- 10.2 ml/min) on a low-protein diet (0.6 g of protein /kg BW/day and energy intake 140 kJ/kg BW/day) for a period of one month were included. Subsequently, this low protein diet was supplemented with keto acids-amino acids at a dose of 0.1 g/kg BW/day orally for a period of 3 months. Examinations performed at baseline and at the end of the follow-up period revealed significant increase in the serum levels of BCAA leucine (p < 0.02), isoleucine (p < 0.03), and valine (p < 0.02) while their renal fractional excretion declined (p < 0.02, p < 0.01 resp.). Keto acid-amino acid administration had no effect on renal function and on the clearance of inulin, para-aminohippuric acid. Endogenous creatinine and urea clearance remained unaltered. A significant correlation between fractional excretion of sodium and leucine (p < 0.05) and a hyperbolic relationship between inulin clearance and fractional excretion of BCAA (p < 0.01) were seen. Moreover, a significant decrease in proteinuria (p < 0.02), plasma urea concentration and renal urea excretion and a rise in albumin level (p < 0.03) were noted. We conclude that in patients with CRI on a low protein diet the supplementation of keto acids-amino acids does not affect renal hemodynamics, but is associated--despite increases in plasma concentrations--with a reduction of renal amino acid and protein excretion suggesting induction of alterations in the tubular transport mechanisms.

  17. Turbine Engine Clearance Control Systems: Current Practices and Future Directions

    NASA Astrophysics Data System (ADS)

    Lattime, Scott B.; Steinetz, Bruce M.

    2002-09-01

    Improved blade tip sealing in the high pressure compressor (HPC) and high pressure turbine (HPT) can provide dramatic reductions in specific fuel consumption (SFC), time-on-wing, compressor stall margin, and engine efficiency as well as increased payload and mission range capabilities. Maintenance costs to overhaul large commercial gas turbine engines can easily exceed 1M. Engine removal from service is primarily due to spent exhaust gas temperature (EGT) margin caused mainly by the deterioration of HPT components. Increased blade tip clearance is a major factor in hot section component degradation. As engine designs continue to push the performance envelope with fewer parts and the market drives manufacturers to increase service life, the need for advanced sealing continues to grow. A review of aero gas turbine engine HPT performance degradation and the mechanisms that promote these losses are discussed. Benefits to the HPT due to improved clearance management are identified. Past and present sealing technologies are presented along with specifications for next generation engine clearance control systems.

  18. Turbine Engine Clearance Control Systems: Current Practices and Future Directions

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Steinetz, Bruce M.

    2002-01-01

    Improved blade tip sealing in the high pressure compressor (HPC) and high pressure turbine (HPT) can provide dramatic reductions in specific fuel consumption (SFC), time-on-wing, compressor stall margin, and engine efficiency as well as increased payload and mission range capabilities. Maintenance costs to overhaul large commercial gas turbine engines can easily exceed $1M. Engine removal from service is primarily due to spent exhaust gas temperature (EGT) margin caused mainly by the deterioration of HPT components. Increased blade tip clearance is a major factor in hot section component degradation. As engine designs continue to push the performance envelope with fewer parts and the market drives manufacturers to increase service life, the need for advanced sealing continues to grow. A review of aero gas turbine engine HPT performance degradation and the mechanisms that promote these losses are discussed. Benefits to the HPT due to improved clearance management are identified. Past and present sealing technologies are presented along with specifications for next generation engine clearance control systems.

  19. CF6 High Pressure Compressor and Turbine Clearance Evaluations

    NASA Technical Reports Server (NTRS)

    Radomski, M. A.; Cline, L. D.

    1981-01-01

    In the CF6 Jet Engine Diagnostics Program the causes of performance degradation were determined for each component of revenue service engines. It was found that a significant contribution to performance degradation was caused by increased airfoil tip radial clearances in the high pressure compressor and turbine areas. Since the influence of these clearances on engine performance and fuel consumption is significant, it is important to accurately establish these relatonships. It is equally important to understand the causes of clearance deterioration so that they can be reduced or eliminated. The results of factory engine tests run to enhance the understanding of the high pressure compressor and turbine clearance effects on performance are described. The causes of clearance deterioration are indicated and potential improvements in clearance control are discussed.

  20. Nasal deposition and clearance in man: comparison of a bidirectional powder device and a traditional liquid spray pump.

    PubMed

    Djupesland, Per Gisle; Skretting, Arne

    2012-10-01

    Delivery of powder formulations to the nose is an attractive alternative for many drugs and vaccines. This study compared the regional nasal deposition and clearance patterns of lactose powder delivered by the OptiNose powder device (Opt-Powder; OptiNose US Inc., Yardley, PA, USA) to that of liquid aerosol administered via a traditional hand-actuated liquid spray pump (Rexam SP270, Rexam Pharma, France). The study was an open-label, crossover design in seven healthy subjects (five females, two males). The regional nasal deposition and clearance patterns of the Opt-Powder device were compared to a traditional liquid spray pump by dynamic gamma camera imaging after administration of either (99m)Tc-labeled lactose powder or liquid (99m)Tc- diethelyne triamine pentaacetic acid-aerosol. The gamma camera images were scaled and aligned with sagittal magnetic resonance images to identify nasal regions. Possible deposition of radiolabeled material in the lungs following both methods of delivery was also evaluated. Both powder and spray were distributed to all of the nasal regions. The Opt-Powder device, however, achieved significantly larger initial deposition in the upper and middle posterior regions of the nose than spray (upper posterior region; Opt-Powder 18.3% ± 11.5 vs. Spray 2.4% ± 1.8, p<0.02; sum of upper and middle posterior regions; Opt-Powder 53.5% ± 18.5 vs. Spray 15.7% ± 13.8, p<0.02). The summed initial deposition to the lower anterior and posterior regions for spray was three times higher compared to Opt-Powder (Opt-Powder 17.4% ± 24.5 vs. Spray 59.4% ± 18.2, p<0.04). OptiNose powder delivery resulted in more rapid overall nasal clearance. No lung deposition was observed. The initial deposition following powder delivery was significantly larger in the ciliated mucosa of the upper and posterior nasal regions, whereas less was deposited in the lower regions. Overall nasal clearance of powder was slower initially, but due to retention in anterior

  1. Prediction of two-sample (99m)Tc-diethylene triamine pentaacetic acid plasma clearance from single-sample method.

    PubMed

    Zuo, Li; Ying-Chun; Wang, Mei; Zhang, Chun-Li; Wang, Rong-Fu; Wang, Hai-Yan

    2005-07-01

    To develop an equation to predict dual plasma sample method (DPSM) (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate (99m)Tc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate (99m)Tc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 +/- 15.5 years and 67.2 +/- 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 +/- 36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was > or =30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/1

  2. Measurement method of rotation angle and clearance in intelligent spherical hinge

    NASA Astrophysics Data System (ADS)

    Hu, Penghao; Lu, Yichang; Chen, Shiyi; Hu, Yi; Zhu, Lianqing

    2018-06-01

    Precision ball hinges are widely applied in parallel mechanisms, robotics, and other areas, but their rotation orientation and angle cannot be obtained during passive motion. The simultaneous clearance error in a precision ball hinge’s motion also can not be determined. In this paper we propose an intelligent ball hinge (IBH) that can detect the rotation angle and moving clearance, based on our previous research results. The measurement model was optimized to promote measurement accuracy and resolution, and an optimal design for the IBH’s structure was determined. The experimental data showed that the measurement accuracy and resolution of the modified scheme were improved. Within  ±10° and  ±  20°, the average errors of the uniaxial measurements were 0.29° and 0.42°, respectively. The resolution of the measurements was 15″. The source of the measurement errors was analyzed through theory and experimental data and several key error sources were determined. A point capacitance model for measuring the clearance error is proposed, which is useful not only in compensating for the angle measurement error but also in realizing the motion clearance of an IBH in real-time.

  3. Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect.

    PubMed

    Bleeker, W K; Teeling, J L; Hack, C E

    2001-11-15

    Recently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the current study, in vivo experiments were performed with mice in which autoantibody production was mimicked by continuous infusion of monoclonal antibodies. In this model, a single dose of IVIG reduced the plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal antibody (mAb) by approximately 40% after 3 days, whereas the concentration of an IgA mAb was not affected. To extrapolate these findings to humans, a computational model for IgG clearance was established that accurately predicted the time course and magnitude of the decrease in IgG plasma levels observed in mice. Adapted for humans, this model predicted a gradually occurring decrease in autoantibody levels after IVIG administration (2 g/kg), with a maximum reduction of approximately 25% after 3 to 4 weeks and a continued decrease of several months. In conclusion, a single high dose of IVIG induces a relatively small but long-lasting reduction of autoantibody levels by accelerated IgG clearance. This mechanism has clinical relevance in the sense that it can fully explain, as the sole mechanism, the gradual decrease in autoantibody levels observed in several patient studies. However, in some clinical studies, larger or more rapid effects have been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as down-regulation of antibody production or neutralization by anti-idiotypic antibodies.

  4. Clearance systems in the brain-implications for Alzheimer disease.

    PubMed

    Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

    2015-08-01

    Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

  5. Clearance systems in the brain—implications for Alzheimer disease

    PubMed Central

    Tarasoff-Conway, Jenna M.; Carare, Roxana O.; Osorio, Ricardo S.; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V.; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J.

    2015-01-01

    Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ. PMID:26195256

  6. Radioaerosol lung clearance in patients with active pulmonary sarcoidosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jacobs, M.P.; Baughman, R.P.; Hughes, J.

    1985-05-01

    Pulmonary radioaerosol clearance rate of /sup 99m/Tc diethylenetriamine pentacetate (DTPA) in 14 patients with untreated sarcoidosis was compared with /sup 67/Ga lung scan and increased lymphocytes in the bronchoalveolar lavage (BAL) fluid. Nine healthy nonsmoking subjects had a mean DTPA clearance rate of 1.18%/min (range, 0.54 to 1.60%/min). Eight of 14 patients with sarcoidosis had clearance rates greater than 1.60%/min. Of those 8 patients with abnormal DTPA clearance, 4 had positive gallium scans, 4 had more than 17% lymphocytes in the BAL fluid, and 3 had both tests positive. To study the cause of abnormal DTPA clearance, 23 subjects (includingmore » 3 normal controls, all 14 patients with sarcoidosis, and 6 patients with localized disease on chest roentgenogram) underwent both DTPA clearance studies and BAL for quantitation of the amount of albumin in lung fluid. There was a positive correlation between the rate of DTPA clearance and the albumin concentration in lung fluid (r = 0.87, p less than 0.01).« less

  7. Intelligent Engine Systems: HPT Clearance Control

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Advanced Thermally Actuated Clearance Control System underwent several studies. Improved flow path isolation quantified what can be gained by making the HPT case nearly adiabatic. The best method of heat transfer was established, and finally two different borrowed air cooling circuits were evaluated to be used for the HPT Active Clearance Control System.

  8. Experimental and computational investigation of the tip clearance flow in a transonic axial compressor rotor

    NASA Astrophysics Data System (ADS)

    Suder, Kenneth L.; Celestina, Mark L.

    1995-06-01

    Experimental and computational techniques are used to investigate tip clearance flows in a transonic axial compressor rotor at design and part speed conditions. Laser anemometer data acquired in the endwall region are presented for operating conditions near peak efficiency and near stall at 100% design speed and at near peak efficiency at 60% design speed. The role of the passage shock/leakage vortex interaction in generating endwall blockage is discussed. As a result of the shock/vortex interaction at design speed, the radial influence of the tip clearance flow extends to 20 times the physical tip clearance height. At part speed, in the absence of the shock, the radial extent is only 5 times the tip clearance height. Both measurements and analysis indicate that under part-speed operating conditions a second vortex, which does not originate from the tip leakage flow, forms in the endwall region within the blade passage and exits the passage near midpitch. Mixing of the leakage vortex with primary flow downstream of the rotor at both design and part speed conditions is also discussed.

  9. Experimental and Computational Investigation of the Tip Clearance Flow in a Transonic Axial Compressor Rotor

    NASA Technical Reports Server (NTRS)

    Suder, Kenneth L.; Celestina, Mark L.

    1995-01-01

    Experimental and computational techniques are used to investigate tip clearance flows in a transonic axial compressor rotor at design and part speed conditions. Laser anemometer data acquired in the endwall region are presented for operating conditions near peak efficiency and near stall at 100% design speed and at near peak efficiency at 60% design speed. The role of the passage shock/leakage vortex interaction in generating endwall blockage is discussed. As a result of the shock/vortex interaction at design speed, the radial influence of the tip clearance flow extends to 20 times the physical tip clearance height. At part speed, in the absence of the shock, the radial extent is only 5 times the tip clearance height. Both measurements and analysis indicate that under part-speed operating conditions a second vortex, which does not originate from the tip leakage flow, forms in the endwall region within the blade passage and exits the passage near midpitch. Mixing of the leakage vortex with primary flow downstream of the rotor at both design and part speed conditions is also discussed.

  10. Dual clearance squeeze film damper

    NASA Technical Reports Server (NTRS)

    Fleming, D. P. (Inventor)

    1985-01-01

    A dual clearance hydrodynamic liquid squeeze film damper for a gas turbine engine is described. Under normal operating conditions, the device functions as a conventional squeeze film damper, using only one of its oil films. When an unbalance reaches abusive levels, as may occur with a blade loss or foreign object damage, a second, larger clearance film becomes active, controlling vibration amplitudes in a near optimum manner until the engine can be safely shut down and repaired.

  11. Controls Considerations for Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.

    2004-01-01

    This presentation discusses active control of turbine tip clearance from a control systems perspective. It is a subset of charts that were presented at the 2003 meeting of the International Society of Air Breathing Engines which was held August 31 through September 5 in Cleveland, Ohio. The associated reference paper is cited at the end of the presentation. The presentation describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, it is believed that the technologies developed as part of this research will benefit a broad spectrum of current and future turbomachinery. The first part of the presentation discusses the concept of tip clearance, problems associated with it, and the benefits of controlling it. It lays out a framework for implementing tip clearance controls that enables the implementation to progress from purely analytical to hardware-in-the-loop to fully experimental. And it briefly discusses how the technologies developed will be married to the previously described ACC Test Rig for hardware-in-the-loop demonstrations. The final portion of the presentation, describes one of the key technologies in some detail by presenting equations and results for a functional dynamic model of the tip clearance phenomena. As shown, the model exhibits many of the clearance dynamics found in commercial gas turbine engines. However, initial attempts to validate the model identified limitations that are being addressed to make the model more realistic.

  12. Cryotherapy for HPV clearance in women with biopsy-confirmed cervical low-grade squamous intraepithelial lesions.

    PubMed

    Chumworathayi, Bandit; Thinkhamrop, Jadsada; Blumenthal, Paul D; Thinkhamrop, Bandit; Pientong, Chamsai; Ekalaksananan, Tipaya

    2010-02-01

    To compare the clearance rate of HPV infection among women aged older than 30 years with biopsy-confirmed cervical low-grade squamous intraepithelial lesions (LSIL) 1 year after cryotherapy with the spontaneous clearance rate (observation). HPV DNA typing by polymerase chain reaction and reverse line blot hybridization were used to identify 14 high-risk types and 23 low-risk types. HPV DNA sequencing was also used for other types. Between December 2007 and March 2009, 100 women were recruited to the study and 60 cases had positive results on HPV testing. Twenty-nine patients were randomly allocated to the cryotherapy group and 31 to the observation group. At 1 year, 89.7% (26/29; 95% CI, 78.6-100%) of the cryotherapy group and 90.3% (28/31; 95% CI, 79.9-100%) of the observation group had negative results on HPV testing (0.6% difference; 95% CI, -15.8 to 14.6%, P=0.94). Cryotherapy failed to increase the clearance of prevalent HPV infections among women with LSIL, although in both arms the clearance rates were above 80%. However, in coupling with visual inspection with acetic acid as a single visit approach, its effect on prevention of HSIL and cervical cancer is still promising. Therefore, cryotherapy should not be withdrawn from such programs. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of increased surface hydrophobicity via drug conjugation on the clearance of inhaled PEGylated polylysine dendrimers.

    PubMed

    Haque, Shadabul; McLeod, Victoria M; Jones, Seth; Fung, Sandy; Whittaker, Michael; McIntosh, Michelle; Pouton, Colin; Owen, David J; Porter, Christopher J H; Kaminskas, Lisa M

    2017-10-01

    PEGylated polylysine dendrimers are attractive and well tolerated inhalable drug delivery platforms that have the potential to control the release, absorption kinetics and lung retention time of conjugated drugs. The clinical application of these systems though, would likely require partial substitution of surface PEG groups with drug molecules that are anticipated to alter their lung clearance kinetics and clearance pathways. In the current study, we therefore evaluated the impact of increased surface hydrophobicity via substitution of 50% surface PEG groups with a model hydrophobic drug (α-carboxyl OtButylated methotrexate) on the lung clearance of a Generation 5 PEGylated polylysine dendrimer in rats. PEG substitution with OtBu-methotrexate accelerated lung clearance of the dendrimer by increasing polylysine scaffold catabolism, improving systemic absorption of the intact dendrimer and low molecular weight products of scaffold catabolism, and enhancing mucociliary clearance. These results suggest that the conjugation of hydrophobic drug on the surface of a PEGylated dendrimer is likely to accelerate lung clearance when compared to a fully PEGylated dendrimer. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  14. 48 CFR 2452.237-75 - Clearance of contractor personnel.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Clearance of contractor... Clauses 2452.237-75 Clearance of contractor personnel. As prescribed in 2437.110(e), insert the following clause in solicitations and contracts. Clearance of Contractor Personnel (OCT 1999) (a) General. This...

  15. Railway clearance intrusion detection method with binocular stereo vision

    NASA Astrophysics Data System (ADS)

    Zhou, Xingfang; Guo, Baoqing; Wei, Wei

    2018-03-01

    In the stage of railway construction and operation, objects intruding railway clearance greatly threaten the safety of railway operation. Real-time intrusion detection is of great importance. For the shortcomings of depth insensitive and shadow interference of single image method, an intrusion detection method with binocular stereo vision is proposed to reconstruct the 3D scene for locating the objects and judging clearance intrusion. The binocular cameras are calibrated with Zhang Zhengyou's method. In order to improve the 3D reconstruction speed, a suspicious region is firstly determined by background difference method of a single camera's image sequences. The image rectification, stereo matching and 3D reconstruction process are only executed when there is a suspicious region. A transformation matrix from Camera Coordinate System(CCS) to Track Coordinate System(TCS) is computed with gauge constant and used to transfer the 3D point clouds into the TCS, then the 3D point clouds are used to calculate the object position and intrusion in TCS. The experiments in railway scene show that the position precision is better than 10mm. It is an effective way for clearance intrusion detection and can satisfy the requirement of railway application.

  16. Enhancement of renal excretion of uric acid during long-term thiazide therapy.

    PubMed

    Pak, C Y; Tolentino, R; Stewart, A; Galosy, R A

    1978-11-01

    The effect of thiazide (hydrochlorothiazide 100 mg per day orally in two divided doses for up to 3 years) on uric acid metabolism was examined in 21 patients with renal stones suffering from renal hypercalciuria or absorptive hypercalciuria. Serum concentration of uric acid increased during thiazide therapy in every patient. In 12 of 21 patients, there was a transient or persistent rise in urinary uric acid of more than 50 mg per day during treatment. The mean urinary uric acid produced by thiazide was positively correlated with the change in the renal clearance of uric acid. Thus, an increase in urinary uric acid was often associated with a rise in uric acid clearance. The results suggest that thiazide may either increase the production of uric acid or decrease the extrarenal disposal of uric acid, in some patients.

  17. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  18. 30 CFR 57.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  19. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  20. 30 CFR 57.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  1. 30 CFR 57.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  2. 30 CFR 57.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  3. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  4. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  5. 30 CFR 57.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Warning devices for restricted clearances. 57... Loading and Dumping Sites § 57.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  6. 30 CFR 56.9306 - Warning devices for restricted clearances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Warning devices for restricted clearances. 56... Loading and Dumping Sites § 56.9306 Warning devices for restricted clearances. Where restricted clearance creates a hazard to persons on mobile equipment, warning devices shall be installed in advance of the...

  7. Selectively increasing the clearance of protein-bound uremic solutes

    PubMed Central

    Luo, Frank J.-G.; Plummer, Natalie S.; Hostetter, Thomas H.; Meyer, Timothy W.

    2012-01-01

    Background. The toxicity of bound solutes could be better evaluated if we could adjust the clearance of such solutes independent of unbound solutes. This study assessed whether bound solute clearances can be increased while maintaining urea clearance constant during the extended hours of nocturnal dialysis. Methods. Nine patients on thrice-weekly nocturnal dialysis underwent two experimental dialysis treatments 1 week apart. The experimental treatments were designed to provide the same urea clearance while providing widely different bound solute clearance. One treatment employed a large dialyzer and high dialyzate flow rate (Qd) of 800 mL/min while blood flow (Qb) was 270 mL/min. The other treatment employed a smaller dialyzer and Qd of 300 mL/min while Qb was 350 mL/min. Results. Treatment with the large dialyzer and higher Qd greatly increased the clearances of the bound solutes p-cresol sulfate (PCS: 27 ± 9 versus 14 ± 6 mL/min) and indoxyl sulfate (IS: 26 ± 8 versus 14 ± 5 mL/min) without altering the clearance of urea (204 ± 20 versus 193 ± 16 mL/min). Increasing PCS and IS clearances increased the removal of these solutes (PCS: 375 ± 200 versus 207 ± 86 mg/session; IS: 201 ± 137 versus 153 ± 74 mg/session), while urea removal was not different. Conclusions. The removal of bound solutes can thus be increased by raising the dialyzate flow and dialyzer size above the low levels sufficient to achieve target Kt/Vurea during extended treatment. Selectively increasing the clearance of bound solutes provides a potential means to test their toxicity. PMID:22231033

  8. Circadian Clearance of a Fungal Pathogen from the Lung Is Not Based on Cell-intrinsic Macrophage Rhythms.

    PubMed

    Chen, Shan; Fuller, Kevin K; Dunlap, Jay C; Loros, Jennifer J

    2018-02-01

    Circadian rhythms govern immune cell function, giving rise to time-of-day variation in the recognition and clearance of bacterial or viral pathogens; to date, however, no such regulation of the host-fungal interaction has been described. In this report, we use murine models to explore circadian control of either fungal-macrophage interactions in vitro or pathogen clearance from the lung in vivo. First, we show that expression of the important fungal pattern recognition receptor Dectin-1 ( clec7a), from either bone marrow-derived or peritoneum-derived macrophages, is not under circadian regulation at either the level of transcript or cell surface protein expression. Consistent with this finding, the phagocytic activity of macrophages in culture against spores of the pathogen Aspergillus fumigatus also did not vary over time. To account for the multiple cell types and processes that may be coordinated in a circadian fashion in vivo, we examined the clearance of A. fumigatus from the lungs of immunocompetent mice. Interestingly, animals inoculated at night demonstrated a 2-fold enhancement in clearance compared with animals inoculated in the morning. Taken together, our data suggest that while molecular recognition of fungi by immune cells may not be circadian, other processes in vivo may still allow for time-of-day differences in fungal clearance from the lung.

  9. Lung-clearance classification of radionuclides in calcined phosphate rock dust

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kalkwarf, D.R.; Jackson, P.O.

    1984-08-01

    Lung-clearance classifications for /sup 210/Pb and /sup 210/Po in airborne dust from elemental phosphorus plants were estimated for use with the lung clearance model proposed by the ICRP Task Group on Lung Dynamics. Estimates were based on measurements of dissolution rates for these radionuclides from sized dust samples into simulated lung fluid at 37/sup 0/C. The estimates were expressed in the classification terms of the model, i.e., D, W and Y, indicating lung clearance half-times of 0 to 10 days, 11 to 100 days and more than 100 days. Dust samples were obtained from two plants in the western Unitedmore » States, and dissolution trials were conducted on fractions containing particles with aerodynamic equivalent diameters (AED) of 0 to 3 ..mu..m and of 3 to 10 ..mu..m. The /sup 210/Pb and /sup 210/Po in each of these fractions were classified 100% Class Y. The specific activities of both radionuclides increased with decreasing AED of the particles. 11 references, 1 figure, 4 tables.« less

  10. 14 CFR § 1260.63 - Customs clearance and visas.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Customs clearance and visas. § 1260.63... COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas (For grants or cooperative agreements with foreign organizations, this clause will be developed on...

  11. Population Pharmacokinetics of Rifapentine and Desacetyl Rifapentine in Healthy Volunteers: Nonlinearities in Clearance and Bioavailability

    PubMed Central

    Lu, Yanhui; Bliven-Sizemore, Erin; Weiner, Marc; Nuermberger, Eric; Burman, William; Dorman, Susan E.; Dooley, Kelly E.

    2014-01-01

    Rifapentine is under active investigation as a potent drug that may help shorten the tuberculosis (TB) treatment duration. A previous rifapentine dose escalation study with daily dosing indicated a possible decrease in bioavailability as the dose increased and an increase in clearance over time for rifapentine and its active metabolite, desacetyl rifapentine. This study aimed to assess the effects of increasing doses on rifapentine absorption and bioavailability and to evaluate the clearance changes over 14 days. A population analysis was performed with nonlinear mixed-effects modeling. Absorption, time-varying clearance, bioavailability, and empirical and semimechanistic autoinduction models were investigated. A one-compartment model linked to a transit compartment absorption model best described the data. The bioavailability of rifapentine decreased linearly by 2.5% for each 100-mg increase in dose. The autoinduction model suggested a dose-independent linear increase in clearance of the parent drug and metabolite over time from 1.2 and 3.1 liters · h−1, respectively, after a single dose to 2.2 and 5.0 liters · h−1, respectively, after 14 once-daily doses, with no plateau being reached by day 14. In clinical trial simulations using the final model, rifapentine demonstrated less-than-dose-proportional pharmacokinetics, but there was no plateau in exposures over the dose range tested (450 to 1,800 mg), and divided dosing increased exposures significantly. Thus, the proposed compartmental model incorporating daily dosing of rifapentine over a wide range of doses and time-related changes in bioavailability and clearance provides a useful tool for estimation of drug exposure that can be used to optimize rifapentine dosing for TB treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01162486.) PMID:24614383

  12. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... transported in-bond, or when they have unentered foreign merchandise aboard. For the purposes of the vessel clearance requirements, merchandise transported in-bond does not include bonded ship's stores or supplies. While American vessels transporting unentered foreign merchandise must fully comply with usual clearance...

  13. 48 CFR 952.204-73 - Facility clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

  14. 48 CFR 952.204-73 - Facility clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

  15. 48 CFR 952.204-73 - Facility clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

  16. 48 CFR 952.204-73 - Facility clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

  17. 48 CFR 952.204-73 - Facility clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....204-73 Section 952.204-73 Federal Acquisition Regulations System DEPARTMENT OF ENERGY CLAUSES AND... granted by the Secretary of Energy. In addition, a Facility Clearance and foreign ownership, control and... Department of Energy Facility Clearance generally need not resubmit the following foreign ownership...

  18. Clinical review: Drug metabolism and nonrenal clearance in acute kidney injury

    PubMed Central

    Vilay, A Mary; Churchwell, Mariann D; Mueller, Bruce A

    2008-01-01

    Decreased renal drug clearance is an obvious consequence of acute kidney injury (AKI). However, there is growing evidence to suggest that nonrenal drug clearance is also affected. Data derived from human and animal studies suggest that hepatic drug metabolism and transporter function are components of nonrenal clearance affected by AKI. Acute kidney injury may also impair the clearance of formed metabolites. The fact that AKI does not solely influence kidney function may have important implications for drug dosing, not only of renally eliminated drugs but also of those that are hepatically cleared. A review of the literature addressing the topic of drug metabolism and clearance alterations in AKI reveals that changes in nonrenal clearance are highly complicated and poorly studied, but they may be quite common. At present, our understanding of how AKI affects drug metabolism and nonrenal clearance is limited. However, based on the available evidence, clinicians should be cognizant that even hepatically eliminated drugs and formed drug metabolites may accumulate during AKI, and renal replacement therapy may affect nonrenal clearance as well as drug metabolite clearance. PMID:19040780

  19. The effects of topical agents of fluticasone propionate, oxymetazoline, and 3% and 0.9% sodium chloride solutions on mucociliary clearance in the therapy of acute bacterial rhinosinusitis in vivo.

    PubMed

    Inanli, Selçuk; Oztürk, Ozmen; Korkmaz, Mukadder; Tutkun, Alper; Batman, Cağlar

    2002-02-01

    The aims of the study were to determine: 1) how mucociliary activity in acute bacterial rhinosinusitis is affected; 2) how this activity is changed by therapy; 3) the effects of topical agents on mucociliary clearance, and 4) the most appropriate topical agent(s) to be used in the therapy of sinusitis. Five groups of patients with acute bacterial rhinosinusitis were studied prospectively. All patients had 500 mg oral amoxicillin and 125 mg oral clavulanic acid preparations given three times daily for 3 weeks. According to the topical agent applications, these groups included: group I (n = 12), no topical treatment was given; group II (n = 14), two puffs for each nostril once daily of 50 microg/100 mL fluticasone propionate was given; group III (n = 9), one puff for each nostril three times daily of 0.05% oxymetazoline was given; group IV (n =12), 3% sodium chloride (NaCl) (buffered to pH 6.5-7 at room temperature) was given; and group V (n =13), 10-mL solutions of 0.9% NaCl (buffered to pH 6.5--7 at room temperature) were given for nasal irrigations three times daily. All patients had medication for 3 weeks and were controlled each week. The saccharin method was used to measure nasal mucociliary clearance. To investigate the early effects of the topical agents for groups II to V, an additional test was repeated 20 minutes after the basal mucociliary clearance recordings. The test was repeated in the first, second, and third weeks of the treatment. The mucociliary clearance was significantly slower in the acute bacterial rhinosinusitis group than in the control group. There was no significant difference between the basal mucociliary clearance and the 20th minute mucociliary clearance of the fluticasone propionate and 0.9% NaCl solution groups. The mean values of the basal and the 20 minute's mucociliary clearance of the oxymetazoline group were 24.72 +/- 6.16 and 15.5 +/- 7.45 minutes, respectively, which were statistically significant. The mean values of the basal

  20. Enhancement of tumor-to-nontumor localization ratios by hepatocyte-directed blood clearance of antibodies labeled with certain residualizing radiolabels.

    PubMed

    Patel, S; Stein, R; Ong, G L; Goldenberg, D M; Mattes, M J

    1999-08-01

    To increase tumor-to-nontumor localization ratios of injected radiolabeled antibodies (Abs), several interrelated methods were used. The model systems used were two human carcinoma xenografts grown in nude mice, targeted by antibodies RS11 (antiepithelial glycoprotein-2) or MN-14 (anticarcinoembryonic antigen). The Abs were conjugated with biotin and 111In-benzyl diethylenetriamine pentaacetic acid, and, at various times after injection, were cleared by intraperitoneal injection of galactosylated streptavidin, which delivers the complexes to hepatocytes. The radiolabel used was selected because it is retained within tumors after catabolism of the Ab by the tumor cell but is quite rapidly excreted from hepatocytes into bile. With blood clearance induced at 24 h, and dissection 5 h later, high tumor-to-nontumor ratios were attained. Depending on the model used, tumor-to-blood ratios were 16:1 to 31:1, and tumor-to-nontumor ratios for the kidney, lungs and bone were also high and greatly increased by the clearance regimen. Despite clearance into the liver, tumor-to-liver ratios remained >1, due to fairly rapid biliary excretion of the label. The absolute antibody uptake by the tumors was also high, because 24 h was allowed for the Ab to penetrate and bind to cells within the subcutaneous tumors. The method described produced high tumor-to-nontumor ratios at 1 d after injection and may be advantageous for tumor imaging with antibodies. Radiation dosimetry calculations indicate that there is only a slight advantage with this approach for radioimmunotherapy.

  1. Numerical investigation of hub clearance flow in a Kaplan turbine

    NASA Astrophysics Data System (ADS)

    Wu, H.; Feng, J. J.; Wu, G. K.; Luo, X. Q.

    2012-11-01

    In this paper, the flow field considering the hub clearance flow in a Kaplan turbine has been investigated through using the commercial CFD code ANSYS CFX based on high-quality structured grids generated by ANSYS ICEM CFD. The turbulence is simulated by k-ω based shear stress transport (SST) turbulence model together with automatic near wall treatments. Four kinds of simulations have been conducted for the runner geometry without hub clearance, with only the hub front clearance, with only the rear hub clearance, and with both front and rear clearance. The analysis of the obtained results is focused on the flow structure of the hub clearance flow, the effect on the turbine performance including hydraulic efficiency and cavitation performance, which can improve the understanding on the flow field in a Kaplan turbine.

  2. The EVERT (effective verruca treatments) trial protocol: a randomised controlled trial to evaluate cryotherapy versus salicylic acid for the treatment of verrucae.

    PubMed

    Cockayne, E Sarah

    2010-02-08

    Verrucae are a common, infectious and sometimes painful problem. The optimal treatment for verrucae is unclear due to a lack of high quality randomised controlled trials. The primary objective of this study is to compare the clinical effectiveness of two common treatments for verrucae: cryotherapy using liquid nitrogen versus salicylic acid. Secondary objectives include a comparison of the cost-effectiveness of the treatments, and an investigation of time to clearance of verrucae, recurrence/clearance of verrucae at six months, patient satisfaction with treatment, pain associated with treatment, and use of painkillers for the treatments. This is an open, pragmatic, multicentre, randomised controlled trial with two parallel groups: cryotherapy using liquid nitrogen delivered by a healthcare professional for a maximum of 4 treatments (treatments 2-3 weeks apart) or daily self-treatment with 50% salicylic acid for a maximum of 8 weeks. Two hundred and sixty-six patients aged 12 years and over with a verruca are being enrolled into the study. The primary outcome is complete clearance of all verrucae as observed on digital photographs taken at 12 weeks compared with baseline and assessed by an independent healthcare professional. Secondary outcomes include self-reported time to clearance of verrucae, self-reported clearance of verrucae at 6 months, cost-effectiveness of the treatments compared to one another, and patient acceptability of both treatments including possible side effects such as pain. The primary analysis will be intention to treat. It is planned that recruitment will be completed by December 2009 and results will be available by June 2010. Current Controlled Trials ISRCTN18994246.

  3. Surface code—biophysical signals for apoptotic cell clearance

    NASA Astrophysics Data System (ADS)

    Biermann, Mona; Maueröder, Christian; Brauner, Jan M.; Chaurio, Ricardo; Janko, Christina; Herrmann, Martin; Muñoz, Luis E.

    2013-12-01

    Apoptotic cell death and the clearance of dying cells play an important and physiological role in embryonic development and normal tissue turnover. In contrast to necrosis, apoptosis proceeds in an anti-inflammatory manner. It is orchestrated by the timed release and/or exposure of so-called ‘find-me’, ‘eat me’ and ‘tolerate me’ signals. Mononuclear phagocytes are attracted by various ‘find-me’ signals, including proteins, nucleotides, and phospholipids released by the dying cell, whereas the involvement of granulocytes is prevented via ‘stay away’ signals. The exposure of anionic phospholipids like phosphatidylserine (PS) by apoptotic cells on the outer leaflet of the plasma membrane is one of the main ‘eat me’ signals. PS is recognized by a number of innate receptors as well as by soluble bridging molecules on the surface of phagocytes. Importantly, phagocytes are able to discriminate between viable and apoptotic cells both exposing PS. Due to cytoskeleton remodeling PS has a higher lateral mobility on the surfaces of apoptotic cells thereby promoting receptor clustering on the phagocyte. PS not only plays an important role in the engulfment process, but also acts as ‘tolerate me’ signal inducing the release of anti-inflammatory cytokines by phagocytes. An efficient and fast clearance of apoptotic cells is required to prevent secondary necrosis and leakage of intracellular danger signals into the surrounding tissue. Failure or prolongation of the clearance process leads to the release of intracellular antigens into the periphery provoking inflammation and development of systemic inflammatory autoimmune disease like systemic lupus erythematosus. Here we review the current findings concerning apoptosis-inducing pathways, important players of apoptotic cell recognition and clearance as well as the role of membrane remodeling in the engulfment of apoptotic cells by phagocytes.

  4. Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

    2009-01-01

    The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high-temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short-range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a benchtop calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

  5. Testing of a Microwave Blade Tip Clearance Sensor at the NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Woike, Mark R.; Roeder, James W.; Hughes, Christopher E.; Bencic, Timothy J.

    2009-01-01

    The development of new active tip clearance control and structural health monitoring schemes in turbine engines and other types of rotating machinery requires sensors that are highly accurate and can operate in a high temperature environment. The use of a microwave sensor to acquire blade tip clearance and tip timing measurements is being explored at the NASA Glenn Research Center. The microwave blade tip clearance sensor works on principles that are very similar to a short range radar system. The sensor sends a continuous microwave signal towards a target and measures the reflected signal. The phase difference of the reflected signal is directly proportional to the distance between the sensor and the target being measured. This type of sensor is beneficial in that it has the ability to operate at extremely high temperatures and is unaffected by contaminants that may be present in turbine engines. The use of microwave sensors for this application is a new concept. Techniques on calibrating the sensors along with installation effects are not well quantified as they are for other sensor technologies. Developing calibration techniques and evaluating installation effects are essential in using these sensors to make tip clearance and tip timing measurements. As a means of better understanding these issues, the microwave sensors were used on a bench top calibration rig, a large axial vane fan, and a turbofan. Background on the microwave tip clearance sensor, an overview of their calibration, and the results from their use on the axial vane fan and the turbofan will be presented in this paper.

  6. Clearance of chrysotile asbestos from human lung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Churg, A.; DePaoli, L.

    1988-01-01

    In contrast to amphibole asbestos, chrysotile asbestos fails to accumulate in human lungs. The reason for this phenomenon is not known. To examine this problem, we extracted chrysotile and tremolite fibers from the lungs of 11 chrysotile miners and millers whose last exposure was within 2 years of death and 12 chrysotile miners and millers whose last exposure was greater than 12 years (7 with last exposure 12-15 years and 5 with last exposure 22-25 years) before death. Fibers were extracted by bleach digestion, and concentrations, compositions, and sizes were determined by analytical electron microscopy. Native UICC Canadian chrysotile wasmore » used as a composition standard. Compared to the standard, there was minor loss of magnesium at 2 years and additional very slight loss after 12 years. The ratio of chrysotile to tremolite concentration did not change with time. There was also no evidence of increasing fiber length with time from last exposure. These data indicate that accumulation of amphibole compared to chrysotile in human lungs does not reflect either long-term dissolution of chrysotile or long-term preferential clearance of chrysotile compared to amphibole. Contrary to results of animal studies, fiber length in humans does not increase with time since last exposure. These findings imply that the failure of chrysotile to accumulate in human lungs reflects events that occur early after exposure rather than long-term clearance mechanisms.« less

  7. Modified Augmented Renal Clearance Score Predicts Rapid Piperacillin and Tazobactam Clearance in Critically Ill Surgery and Trauma Patients

    DTIC Science & Technology

    2014-04-24

    intermittent dosing regimens. CONCLUSION: Given its ability to predict antimicrobial clearance above populationmedians, which could compromise therapy, the...campaign dedicated to improve out- comes.1,2 In the era ofmultiply drug- resistant pathogens and rising antimicrobial minimum inhibitory concentrations (MICs...urinary creatinine clearance significantly exceeds what is predicted by the serum creatinine concentration according to various mathematical

  8. Advanced optical blade tip clearance measurement system

    NASA Technical Reports Server (NTRS)

    Ford, M. J.; Honeycutt, R. E.; Nordlund, R. E.; Robinson, W. W.

    1978-01-01

    An advanced electro-optical system was developed to measure single blade tip clearances and average blade tip clearances between a rotor and its gas path seal in an operating gas turbine engine. This system is applicable to fan, compressor, and turbine blade tip clearance measurement requirements, and the system probe is particularly suitable for operation in the extreme turbine environment. A study of optical properties of blade tips was conducted to establish measurement system application limitations. A series of laboratory tests was conducted to determine the measurement system's operational performance characteristics and to demonstrate system capability under simulated operating gas turbine environmental conditions. Operational and environmental performance test data are presented.

  9. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

  10. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

  11. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

  12. 19 CFR 4.61 - Requirements for clearance.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Requirements for clearance. 4.61 Section 4.61 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE... made by filing Customs Form 1300 (Vessel Entrance or Clearance Statement) executed by the vessel master...

  13. The role of astrocytes in amyloid β-protein toxicity and clearance.

    PubMed

    Thal, Dietmar Rudolf

    2012-07-01

    The deposition of the amyloid β-protein (Aβ) in the brain is a pathological hallmark of Alzheimer's disease (AD). Here, Aβ deposits occur as Aβ plaques in the brain parenchyma and in the walls of cerebral and leptomeningeal blood vessels. Astrocytes are considered to be involved in the clearance of Aβ from the brain parenchyma into the perivascular space, across the blood-brain barrier, or by enzymatic degradation. As such it has been assumed that clearance of Aβ by astrocytes is beneficial. In a recent study published in Experimental Neurology Mulder et al. (2012; 233: 373-379) report changes in neprilysin and scavenger receptor class B member 1 gene expression in astrocytes exposed to fibrillar Aβ depending on the availability of amyloid-associated proteins, especially apolipoprotein E (apoE). Astrocytes from AD patients did not show this response in gene expression. Reactive astrocytes and Aβ containing astrocytes are common findings in the AD brain. A loss of excitatory amino acid transporter 2 expression in perivascular astrocytes of APOE ε4-positive AD cases and an alteration of neuronal apoE metabolism in the event of perivascular drainage of apoE-Aβ complexes has also been described. As such, reactive and compensatory changes in AD astrocytes compete with supporting functions of astrocytes finally leading to an impairment of metabolic support and transmitter recycling in the brain. In summary, exposure of astrocytes to increased amounts of Aβ over a long period in time very likely impairs the above mentioned supporting functions of astrocytes in AD patients because these cells have to clear large amounts of Aβ and, thereby, neglect their other functions. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Histaminergic regulation of natural killer cell-mediated clearance of tumour cells in mice.

    PubMed

    Asea, A; Hermodsson, S; Hellstrand, K

    1996-01-01

    Treatment of Swiss albino mice with histamine enhanced the clearance of natural killer (NK)-cell sensitive YAC-1 lymphoma and B16/F10 melanoma cells from lung tissue in vivo, but did not affect the elimination of NK-cell-insensitive P815 mastocytoma cells. The effect of histamine was apparently mediated by H2-type histamine receptors (H2R) since it was blocked by ranitidine, and H2R antagonist. Histamine did not affect clearance of tumour cells in animals depleted of NK cells in vivo by treatment with antibodies to asialo-GM1 or NK1.1. The effect of histamine was time-dependent: pretreatment with histamine for 3 h significantly augmented the clearance of YAC-1 cells, whereas, pretreatment with histamine for 5 min was ineffective. Histamine potentiated the anti-tumour properties of NK-cell activators such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha) in vivo. None of these lymphokines significantly affected the clearance of YAC-1 cells unless animals were concomitantly treated with histamine. Treatment with ranitidine alone reduced the in vivo clearance of YAC-1 cells from lungs but did not affect the clearance of NK-cell-insensitive P815 cells. Effects of ranitidine on NK-cell function in vivo were not shared by a chemical control to ranitidine, AH20239AA, thus indicating that the inhibition of NK-cells results from H2R antagonism rather than non-specific toxicity. It is concluded that histaminergic mechanisms may be involved in the regulation of NK cell function in vivo.

  15. Adequacy of peritoneal dialysis: beyond small solute clearance.

    PubMed

    Goldberg, Ryan; Yalavarthy, Rajesh; Teitelbaum, Isaac

    2009-01-01

    Peritoneal dialysis adequacy is monitored primarily by indices of small solute clearance, Kt/V(urea) and creatinine clearance (C(cr)). Once a threshold of adequacy has been obtained, however, increasing small solute clearance does not result in improved long-term outcomes of PD patients. There are several other factors that may affect optimal dialysis outcomes. These include, but are not limited to: ultrafiltration, inflammation, malnutrition, and mineral metabolism. In this article, we will briefly review data regarding the relationships between these factors and survival on PD.

  16. Lactate clearance as a marker of mortality in pediatric intensive care unit.

    PubMed

    Munde, A; Kumar, N; Beri, R S; Puliyel, J M

    2014-07-01

    To correlate lactate clearance with Pediatric Intensive Care Unit (PICU) mortality. 45 (mean age 40.15 mo, 60% males) consecutive admissions in the PICU were enrolled between May 2012 to June 2013. Lactate clearance (Lactate level at admission - level 6 hr later x 100 / lactate level at admission) in first 6 hours of hospitalization was correlated to in-hospital mortality and PRISM score. Twelve out of 45 patients died. 90% died among those with delayed/poor clearance (clearance <30%) compared to 8.5% in those with good clearance (clearance >30%) (P<0.001). Lactate clearance <30% predicted mortality with sensitivity of 75%, specificity of 97%, positive predictive value of 90%, and negative predictive value of 91.42%. Predictability was comparable to PRISM score >30. Lactate clearance at six hours correlates with mortality in the PICU.

  17. Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome.

    PubMed

    Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Belzberg, H; Wedel, S; Placko, R

    1985-09-01

    The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.

  18. 46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

  19. 46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

  20. 46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

  1. 46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

  2. 46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... worn down to 6.4 mm (0.25 in) clearance for shafts of 229 mm (9 in) or less in diameter, 7.95 mm (0.3125 in) clearance for shafts exceeding 229 mm (9 in) but not exceeding 305 mm (12 in) in diameter, and 9.53 mm (0.375 in) clearance for shafts exceeding 305 mm (12 in) in diameter. (2) Where the...

  3. Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice.

    PubMed

    Jansen, A J Gerard; Josefsson, Emma C; Rumjantseva, Viktoria; Liu, Qiyong Peter; Falet, Hervé; Bergmeier, Wolfgang; Cifuni, Stephen M; Sackstein, Robert; von Andrian, Ulrich H; Wagner, Denisa D; Hartwig, John H; Hoffmeister, Karin M

    2012-02-02

    When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17(ΔZn/ΔZn) platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage.

  4. Further Characterization of an Active Clearance Control Concept

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn C.; Steinetz, Bruce M.; Oswald, Jay J.

    2007-01-01

    A new test chamber and precision hydraulic actuation system were incorporated into an active clearance control (ACC) test rig at NASA Glenn Research Center. Using the improved system, a fast-acting, mechanically-actuated, ACC concept was evaluated at engine simulated temperatures and pressure differentials up to 1140 F and 120 psig, on the basis of secondary seal leakage and kinematic controllability. During testing, the ACC concept tracked a simulated flight clearance transient profile at 1140 F, 120 psig, with a maximum error of only 0.0012 in. Comparison of average dynamic leakage of the system with average static leakage did not show significant differences between the two operating conditions. Calculated effective clearance values for the rig were approximately 0.0002 in. at 120 psig, well below the industry specified effective clearance threshold of 0.001 in.

  5. The levonorgestrel-releasing intrauterine system is associated with delayed endocervical clearance of Chlamydia trachomatis without alterations in vaginal microbiota

    PubMed Central

    Liechty, Emma R.; Bergin, Ingrid L.; Bassis, Christine M.; Chai, Daniel; LeBar, William; Young, Vincent B.; Bell, Jason D.

    2015-01-01

    Progestin-based contraception may impact women's susceptibility to sexually transmitted infection. We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on cervical persistence of Chlamydia trachomatis (CT) in a baboon model. Female olive baboons (Papio anubis) with or without an LNG-IUS received CT or sham inoculations. CT was detected in cervical epithelium with weekly nucleic acid amplification testing (NAAT) and culture. Presence of the LNG-IUS was associated with prolonged persistence of CT. Median time to post-inoculation clearance of CT as detected by NAAT was 10 weeks (range 7–12) for animals with an LNG-IUS and 3 weeks (range 0–12) for non-LNG-IUS animals (P = 0.06). Similarly, median time to post-inoculation clearance of CT by culture was 9 weeks (range 3–12) for LNG-IUS animals and 1.5 weeks (range 0–10) for non-LNG-IUS animals (P = 0.04). We characterized the community structure of the vaginal microbiota with the presence of the LNG-IUS to determine if alterations in CT colonization dynamics were associated with changes in vaginal commensal bacteria. Vaginal swabs were collected weekly for microbiome analysis. Endocervical CT infection was not correlated with alterations in the vaginal microbiota. Together, these results suggest that LNG-IUS may facilitate CT endocervical persistence through a mechanism distinct from vaginal microbial alterations. PMID:26371177

  6. Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats

    PubMed Central

    Uchida, Ryota; Okamoto, Hinako; Ikuta, Naoko; Terao, Keiji; Hirota, Takashi

    2015-01-01

    α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C0), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance. PMID:26402669

  7. Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats.

    PubMed

    Uchida, Ryota; Okamoto, Hinako; Ikuta, Naoko; Terao, Keiji; Hirota, Takashi

    2015-09-21

    α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C₀), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance.

  8. ANSYS-MATLAB co-simulation of mucus flow distribution and clearance effectiveness of a new simulated cough device.

    PubMed

    Ren, Shuai; Shi, Yan; Cai, Maolin; Zhao, Hongmei; Zhang, Zhaozhi; Zhang, Xiaohua Douglas

    2018-06-01

    Coughing is an irritable reaction that protects the respiratory system from infection and improves mucus clearance. However, for the patients who cannot cough autonomously, an assisted cough device is essential for mucus clearance. Considering the low efficiency of current assisted cough devices, a new simulated cough device based on the pneumatic system is proposed in this paper. Given the uncertainty of airflow rates necessary to clear mucus from airways, the computational fluid dynamics Eulerian wall film model and cough efficiency (CE) were used in this study to simulate the cough process and evaluate cough effectiveness. The Ansys-Matlab co-simulation model was set up and verified through experimental studies using Newtonian fluids. Next, model simulations were performed using non-Newtonian fluids, and peak cough flow (PCF) and PCF duration time were analyzed to determine their influence on mucus clearance. CE growth rate (λ) was calculated to reflect the CE variation trend. From the numerical simulation results, we find that CE rises as PCF increases while the growth rate trends to slow as PCF increases; when PCF changes from 60 to 360 L/min, CE changes from 3.2% to 51.5% which is approximately 16 times the initial value. Meanwhile, keeping a long PCF duration time could greatly improve CE under the same cough expired volume and PCF. The results indicated that increasing the PCF and PCF duration time can improve the efficiency of mucus clearance. This paper provides a new approach and a research direction for control strategy in simulated cough devices for airway mucus clearance. Copyright © 2018 John Wiley & Sons, Ltd.

  9. The role of lectins and glycans in platelet clearance

    PubMed Central

    Hoffmeister, Karin M.

    2015-01-01

    Summary In recent years, it has become increasingly apparent that the life span of transfused platelets in circulation is regulated, at least in part, by glycan-lectin mediated mechanisms. There is clear evidence that refrigerated platelets are cleared by glycan-lectin mediated clearance mechanisms. Acute platelet cooling clusters glycoprotein (GP) Ibα receptors bearing uncovered N-acetylglucosamine (GlcNAc), and αMβ2 integrins on hepatic macrophages recognise clustered GlcNAc to rapidly clear these platelets from circulation. With prolonged refrigeration GPIbα clustering bearing uncovered galactose increases, which mediates the removal of long-term refrigerated platelets via hepatic Ashwell-Morell receptors (AMR), originally named as asialoglycoprotein receptors. In contrast, little is known about the molecular mechanisms of transfused room temperature platelet clearance. This review examines the role of glycan-lectin mediated clearance of exogenous, i.e. transfused chilled platelet clearance and briefly addresses the current knowledge of stored platelet function, degradation and its relation to platelet clearance. PMID:21781240

  10. 78 FR 64523 - Agency Information Collection Activities: Vessel Entrance or Clearance Statement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-29

    ... respondents or record keepers from the collection of information (a total capital/startup costs and operations... vessel data at time of formal entrance and clearance in U.S. ports. The form allows the master to attest... Responses per Respondent: 22. Estimated Total Annual Responses: 264,000. Estimated Time per Response: 30...

  11. Automation for "Direct-to" Clearances in Air-Traffic Control

    NASA Technical Reports Server (NTRS)

    Erzberger, Heinz; McNally, David

    2006-01-01

    A method of automation, and a system of computer hardware and software to implement the method, have been invented to assist en-route air-traffic controllers in the issuance of clearances to fly directly to specified waypoints or navigation fixes along straight paths that deviate from previously filed flight plans. Such clearances, called "direct-to" clearances, have been in use since before the invention of this method and system.

  12. Real-time Measurements of Amino Acid and Protein Hydroperoxides Using Coumarin Boronic Acid*

    PubMed Central

    Michalski, Radoslaw; Zielonka, Jacek; Gapys, Ewa; Marcinek, Andrzej; Joseph, Joy; Kalyanaraman, Balaraman

    2014-01-01

    Hydroperoxides of amino acid and amino acid residues (tyrosine, cysteine, tryptophan, and histidine) in proteins are formed during oxidative modification induced by reactive oxygen species. Amino acid hydroperoxides are unstable intermediates that can further propagate oxidative damage in proteins. The existing assays (oxidation of ferrous cation and iodometric assays) cannot be used in real-time measurements. In this study, we show that the profluorescent coumarin boronic acid (CBA) probe reacts with amino acid and protein hydroperoxides to form the corresponding fluorescent product, 7-hydroxycoumarin. 7-Hydroxycoumarin formation was catalase-independent. Based on this observation, we have developed a fluorometric, real-time assay that is adapted to a multiwell plate format. This is the first report showing real-time monitoring of amino acid and protein hydroperoxides using the CBA-based assay. This approach was used to detect protein hydroperoxides in cell lysates obtained from macrophages exposed to visible light and photosensitizer (rose bengal). We also measured the rate constants for the reaction between amino acid hydroperoxides (tyrosyl, tryptophan, and histidine hydroperoxides) and CBA, and these values (7–23 m−1 s−1) were significantly higher than that measured for H2O2 (1.5 m−1 s−1). Using the CBA-based competition kinetics approach, the rate constants for amino acid hydroperoxides with ebselen, a glutathione peroxidase mimic, were also determined, and the values were within the range of 1.1–1.5 × 103 m−1 s−1. Both ebselen and boronates may be used as small molecule scavengers of amino acid and protein hydroperoxides. Here we also show formation of tryptophan hydroperoxide from tryptophan exposed to co-generated fluxes of nitric oxide and superoxide. This observation reveals a new mechanism for amino acid and protein hydroperoxide formation in biological systems. PMID:24928516

  13. Randomized Vehicle-Controlled Study of Short Drug Incubation Aminolevulinic Acid Photodynamic Therapy for Actinic Keratoses of the Face or Scalp.

    PubMed

    Pariser, David M; Houlihan, Anna; Ferdon, Mary Beth; Berg, James E

    2016-03-01

    Aminolevulinic acid photodynamic therapy (ALA-PDT) can be effective and well tolerated when applied over a broad area and for short drug incubation times. To evaluate the effect of short-incubation time and application method on the safety and efficacy of ALA-PDT versus vehicle (VEH-PDT) in the treatment of actinic keratoses (AKs) of the face or scalp. Aminolevulinic acid or VEH was applied to face or scalp as a broad area application for 1, 2, or 3 hours or as a spot application for 2 hours before blue light activation. An identical treatment was repeated at Week 8 if any AK lesions remained. Median AK clearance rate for ALA-treated subjects ranged from 68% to 79% at Week 12, compared with 7% of the VEH-treated group (p < .0001). Complete clearance rate for ALA-treated subjects ranged from 17% (8/46) to 30% (14/47) at Week 12, compared with 2% (1/46) of the VEH-treated group (p = .0041). The safety profile seen in this study is consistent with previously reported side effects of the therapy. Short-incubation ALA-PDT was found to be superior to VEH-PDT for AK lesion clearance. A second treatment improves efficacy.

  14. Effects of folic acid supplementation on the pharmacokinetics and anticoagulant effect of warfarin: an open-label, prospective study of long-term administration in adults.

    PubMed

    Muszkat, Mordechai; Bialer, Omer; Blotnick, Simcha; Adar, Liat; Xie, Hong-Guang; Ufer, Mike; Cascorbi, Ingolf; Caraco, Yoseph

    2010-02-01

    Folic acid supplementation in patients with folic acid deficiency has been associated with increased clearance of phenytoin to its cytochrome P450 (CYP) 2C9-mediated metabolite, 5-(4'-hydroxyphenyl)-5-phenylhydantoin. The aim of this study was to determine whether folic acid supplementation increases the dosage requirement of the CYP2C9 substrate warfarin, and the formation clearance of the CYP2C9-mediated product, (S)-7-hydroxywarfarin. Patients aged >or=18 years with folic acid deficiency who were receiving long-term treatment with a stable dosage of warfarin were studied prospectively, before and 30 to 60 days after the initiation of supplementation with folic acid. Warfarin dosage and international normalized ratio (INR) were documented, and the formation clearance of (S)- and (R)-7-hydroxywarfarin and the oral clearance of (S)- and (R)-warfarin were determined. Twenty-four white patients (14 males; mean (SD) age, 55.0 [19.7] years; body mass index, 30.64 [6.8] kg/m(2)) were enrolled. Treatment with folic acid was associated with a significantly increased mean (SD) formation clearance of (S)-7-hydroxywarfarin (1.096 [0.816] vs 1.608 [1.302] mL/min; P = 0.048). Before folic acid supplementation, the mean (SD) warfarin dosage was 5.98 (2.12) mg/d, and the INR was 2.51 (0.55). During supplementation, the warfarin dosage was 6.17 (2.31) mg/d and the INR was 2.63 (0.65) (both, P = NS vs before supplementation). Folic acid supplementation was associated with significantly increased formation clearance of (S)-7-hydroxywarfarin. Changes in warfarin dosage requirements and INR were nonsignificant. Copyright 2010. Published by EM Inc USA.

  15. Long-term clearance from small airways in patients with cystic fibrosis.

    PubMed

    Lindström, M; Camner, P; Falk, R; Hjelte, L; Philipson, K; Svartengren, M

    2005-02-01

    Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways. Radiolabelled Teflon particles (6 microm) were inhaled with an extremely slow inhalation flow, 0.05 L x s(-1). Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects. The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12-16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase. The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.

  16. Risk factors for symptomatic hypocalcaemia complicating treatment with zoledronic acid.

    PubMed

    Chennuru, S; Koduri, J; Baumann, M A

    2008-08-01

    The bisphosphonate zoledronic acid is commonly prescribed to prevent skeletal complications in patients with multiple myeloma or metastatic cancer. Although symptomatic hypocalcaemia is a potential risk of treatment, it has been thought to be uncommon. After seeing several episodes of symptomatic hypocalcaemia following zoledronic acid administration, we undertook a review to determine the incidence of this complication in our population and to attempt to identify risk factors. We reviewed the records of all patients receiving zoledronic acid in two teaching hospitals over a 2-year period. Findings collected included the indication for treatment, whether dosing was adjusted for creatinine clearance, coadministered medications, serum chemistries and clinical course. Of 120 patients who received a total of 546 zoledronic acid infusions, hypocalcaemia developed related to 55 infusions (10%) in 42 patients (35%). Symptomatic hypocalcaemia requiring i.v. supplementation occurred in 10 patients (8%), in spite of appropriate dose adjustment for creatinine clearance and despite prophylactic administration of oral calcium and vitamin D. More patients who became hypocalcaemic developed impairment of creatinine clearance during zoledronic acid treatment than in the group that remained normocalcaemic. Hypomagnesaemia was found in all patients who developed hypocalcaemia who had serum magnesium measured. Hypocalcaemia was common in our patient group following zoledronic acid treatment. Because of the prolonged elimination half-life of this agent (146 h), renal impairment occurring during a number of days after administration may increase risk. Hypomagnesaemia may further increase risk by blunting compensatory increase in parathyroid hormone secretion.

  17. Clearance detector and method for motion and distance

    DOEpatents

    Xavier, Patrick G [Albuquerque, NM

    2011-08-09

    A method for correct and efficient detection of clearances between three-dimensional bodies in computer-based simulations, where one or both of the volumes is subject to translation and/or rotations. The method conservatively determines of the size of such clearances and whether there is a collision between the bodies. Given two bodies, each of which is undergoing separate motions, the method utilizes bounding-volume hierarchy representations for the two bodies and, mappings and inverse mappings for the motions of the two bodies. The method uses the representations, mappings and direction vectors to determine the directionally furthest locations of points on the convex hulls of the volumes virtually swept by the bodies and hence the clearance between the bodies, without having to calculate the convex hulls of the bodies. The method includes clearance detection for bodies comprising convex geometrical primitives and more specific techniques for bodies comprising convex polyhedra.

  18. 2015 Annual Report on Security Clearance Determinations

    DTIC Science & Technology

    2016-06-28

    completed or pending security clearance determinations for government employees and contractors during the preceding fiscal year that have taken longer...each level during the preceding fiscal year. Similar data pertaining to USG contractors is also required. Also, for each element of the Intelligence...for USG Employees and USG Contractors Security Clearance Determination Processing Metrics for the Seven IC Agencies The number of individuals

  19. Dynamic modelling and experimental study of cantilever beam with clearance

    NASA Astrophysics Data System (ADS)

    Li, B.; Jin, W.; Han, L.; He, Z.

    2012-05-01

    Clearances occur in almost all mechanical systems, typically such as the clearance between slide plate of gun barrel and guide. Therefore, to study the clearances of mechanisms can be very important to increase the working performance and lifetime of mechanisms. In this paper, rigid dynamic modelling of cantilever with clearance was done according to the subject investigated. In the rigid dynamic modelling, clearance is equivalent to the spring-dashpot model, the impact of beam and boundary face was also taken into consideration. In ADAMS software, the dynamic simulation was carried out according to the model above. The software simulated the movement of cantilever with clearance under external excitation. Research found: When the clearance is larger, the force of impact will become larger. In order to study how the stiffness of the cantilever's supporting part influences natural frequency of the system, A Euler beam which is restricted by a draught spring and a torsion spring at its end was raised. Through numerical calculation, the relationship between natural frequency and stiffness was found. When the value of the stiffness is close to the limit value, the corresponding boundary condition is illustrated. An ADAMS experiment was carried out to check the theory and the simulation.

  20. Optimization of protein and peptide drugs based on the mechanisms of kidney clearance.

    PubMed

    Huang, Jiaguo; Wu, Huizi

    2018-05-30

    Development of proteins and peptides into drugs has been considered as a promising strategy to target certain diseases. However, only few proteins and peptides has been approved as new drugs into the market each year. One major problem is that proteins and peptides often exhibit short plasma half-life times, which limits the application for their clinical use. In most cases a short half-life time is not effective to deliver sufficient amount of drugs to the target organs and tissues, which is generally caused by fast renal clearance and low plasma stability due to proteolytic degradation during systemic circulation, because the most common clearance pathway of small proteins and peptides is through glomerular filtration by the kidneys. In this review, enzymatic degradation of proteins and peptides were discussed. Furthermore, several approaches to lengthen the half-life of peptides and proteins drugs based on the unique structures of glomerular capillary wall and the mechanisms of glomerular filtration were summarized, such as increasing the size and hydrodynamic diameter; increasing the negative charge to delay the filtration; increasing plasma protein binding to decrease plasma clearance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Chaos vibration of pinion and rack steering trapezoidal mechanism containing two clearances

    NASA Astrophysics Data System (ADS)

    Wei, Daogao; Wang, Yu; Jiang, Tong; Zheng, Sifa; Zhao, Wenjing; Pan, Zhijie

    2017-08-01

    The multi-clearances of breaking type steering trapezoidal mechanism joints influences vehicle steering stability. Hence, to ascertain the influence of clearance value on steering stability, this paper takes the steering mechanism of a certain vehicle type as a prototype that can be simplified into a planar six-bar linkage, then establishes the system dynamic differential equations after considering the two clearances of tie rods and the steering knuckle arms. The influence of the clearance parameters on the movement stability of the steering mechanism is studied using a numerical computation method. Results show that when the two clearances are equal, the planar movement of the tie rods changes from period-doubling to chaos as the clearances increase. When the two clearances are 0.25 mm and 1.5 mm respectively, the planar movements of the two side tie rods come into chaos, causing the steering stability to deteriorate. Moreover, with the increase of clearances, turning moment fluctuates more intensively and the peak value increases.

  2. 48 CFR 245.7002 - Duties and responsibilities of plant clearance officers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... clearance cases and disposal documents; (e) Initiate screening and provide technical support to screeners in...) Technical and quantitative allocability of property; (g) Ensure the timely shipment or release by the... are minimized and, when necessary, work with the contractor and property administrator to implement...

  3. Calculation of tip clearance effects in a transonic compressor rotor

    NASA Technical Reports Server (NTRS)

    Chima, R. V.

    1996-01-01

    The flow through the tip clearance region of a transonic compressor rotor (NASA rotor 37) was computed and compared to aerodynamic probe and laser anemometer data. Tip clearance effects were modeled both by gridding the clearance gap and by using a simple periodicity model across the ungridded gap. The simple model was run with both the full gap height, and with half the gap height to simulate a vena-contracta effect. Comparisons between computed and measured performance maps and downstream profiles were used to validate the models and to assess the effects of gap height on the simple clearance model. Recommendations were made concerning the use of the simple clearance model. Detailed comparisons were made between the gridded clearance gap solution and the laser anemometer data near the tip at two operating points. The computer results agreed fairly well with the data but overpredicted the extent of the casing separation and underpredicted the wake decay rate. The computations were then used to describe the interaction of the tip vortex, the passage shock, and the casing boundary layer.

  4. A Matter of Millimeters: Defining the Processes for Critical Clearances on Curiosity

    NASA Technical Reports Server (NTRS)

    Florow, Brandon

    2013-01-01

    The Mars Science Laboratory (MSL) mission presents an immense packaging problem in that it takes a rover the size of a car with a sky crane landing system and packs it tightly into a spacecraft. This creates many areas of close and critical clearances. Critical Clearances are defined as hardware-to-hardware or hardware-to-envelope clearances which fall below a pre-established location dependent threshold and pose a risk of hardware to hardware contact during events such as launch, entry, landing, and operations. Close Clearances, on the other hand, are defined as any clearance value that is chosen to be tracked but is larger than the critical clearance threshold for its region. Close clearances may be tracked for various reasons including uncertainty in design, large expected dynamic motion, etc.

  5. Role of Acid and Weakly Acidic Reflux in Gastroesophageal Reflux Disease Off Proton Pump Inhibitor Therapy

    PubMed Central

    Sung, Hea Jung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

    2012-01-01

    Background/Aims Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. Methods We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Results Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [< 1%]). Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. Conclusions In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus. PMID:22837877

  6. Role of Acid and weakly acidic reflux in gastroesophageal reflux disease off proton pump inhibitor therapy.

    PubMed

    Sung, Hea Jung; Cho, Yu Kyung; Moon, Sung Jin; Kim, Jin Su; Lim, Chul Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Choi, Myung-Gye

    2012-07-01

    Available data about reflux patterns and symptom determinants in the gastroesophageal reflux disease (GERD) subtypes off proton pump inhibitor (PPI) therapy are lacking. We aimed to evaluate reflux patterns and determinants of symptom perception in patients with GERD off PPI therapy by impedance-pH monitoring. We retrospectively reviewed the impedance-pH data in patients diagnosed as GERD based on results of impedance-pH monitoring, endoscopy and/or typical symptoms. The characteristics of acid and weakly acidic reflux were evaluated. Symptomatic and asymptomatic reflux were compared according to GERD subtypes and individual symptoms. Forty-two patients (22 males, mean age 46 years) were diagnosed as GERD (17 erosive reflux disease, 9 pH(+) non-erosive reflux disease [NERD], 9 hypersensitive esophagus and 7 symptomatic NERD). A total of 1,725 reflux episodes were detected (855 acid [50%], 857 weakly acidic [50%] and 13 weakly alkaline reflux [< 1%]). Acid reflux was more frequently symptomatic and bolus clearance was longer compared with weakly acidic reflux. In terms of globus, weakly acidic reflux was more symptomatic. Symptomatic reflux was more frequently acid and mixed reflux; these associations were more pronounced in erosive reflux disease and symptomatic NERD. The perception of regurgitation was related to acid reflux, while that of globus was more related to weakly acidic reflux. In patients not taking PPI, acid reflux was more frequently symptomatic and had longer bolus clearance. Symptomatic reflux was more frequently acid and mixed type; however, weakly acidic reflux was associated more with globus. These data suggest a role for impedance-pH data in the evaluation of globus.

  7. Novel lanthanide-labeled metal oxide nanoparticles improve the measurement of in vivo clearance and translocation.

    PubMed

    Abid, Aamir D; Anderson, Donald S; Das, Gautom K; Van Winkle, Laura S; Kennedy, Ian M

    2013-01-10

    The deposition, clearance and translocation of europium-doped gadolinium oxide nanoparticles in a mouse lung were investigated experimentally. Nanoparticles were synthesized by spray flame pyrolysis. The particle size, crystallinity and surface properties were characterized. Following instillation, the concentrations of particles in organs were determined with inductively coupled plasma mass spectrometry. The protein corona coating the nanoparticles was found to be similar to the coating on more environmentally relevant nanoparticles such as iron oxide. Measurements of the solubility of the nanoparticles in surrogates of biological fluids indicated very little propensity for dissolution, and the elemental ratio of particle constituents did not change, adding further support to the contention that intact nanoparticles were measured. The particles were intratracheally instilled into the mouse lung. After 24 hours, the target organs were harvested, acid digested and the nanoparticle mass in each organ was measured by inductively coupled plasma mass spectrometry (ICP-MS). The nanoparticles were detected in all the studied organs at low ppb levels; 59% of the particles remained in the lung. A significant amount of particles was also detected in the feces, suggesting fast clearance mechanisms. The nanoparticle system used in this work is highly suitable for quantitatively determining deposition, transport and clearance of nanoparticles from the lung, providing a quantified measure of delivered dose.

  8. 32 CFR 644.521 - Limitations on clearance cost.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Limitations on clearance cost. 644.521 Section 644.521 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed...

  9. 32 CFR 644.522 - Clearance of military scrap.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644.522 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed...

  10. Sequential assessment of pulmonary epithelial diethylene triamine penta-acetate clearance and intrapulmonary transferrin accumulation during Escherichia coli peritonitis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ishizaka, A.; Stephens, K.E.; Segall, G.M.

    1990-03-01

    The individual roles of pulmonary capillary endothelial and alveolar epithelial permeability in the pathogenesis of the adult respiratory distress syndrome (ARDS) are unclear. We developed a method for the sequential assessment of pulmonary macromolecule accumulation and small solute clearance in vivo using a gamma camera. We measured the exponential clearance coefficient of 111In-labeled diethylene triamine penta-acetate (111In-DTPA) to assess airway clearance of small solutes. We also calculated the exponential equilibration coefficient of 111In-labeled transferrin (111In-TF) to assess intrapulmonary accumulation of transferrin. We determined these parameters in guinea pigs with Escherichia coli peritonitis and compared them with a saline-treated control group,more » oleic-acid-treated groups, and a group treated with low molecular weight dextran Ringer solution. The pulmonary DTPA clearance and the intrapulmonary transferrin accumulation were significantly increased in the peritonitis group (29.4 +/- 8.2 x 10(-3) min-1, p less than 0.02, and 15.1 +/- 3.1 x 10(-3) min-1, p less than 0.02) when compared with the control group (3.1 +/- 0.8 x 10(-3) min-1 and 4.5 +/- 0.5 x 10(-3) min-1). These changes developed within 5.5 h of the initial insult. Neither increased extravascular lung water nor elevated pulmonary artery and left atrial pressures were detected in the peritonitis group. The low molecular weight dextran Ringer group did not show a significant increase in the pulmonary DTPA clearance and the intrapulmonary transferrin accumulation.« less

  11. Comparative Inter-Species Pharmacokinetics of Phenoxyacetic Acid Herbicides and Related Organic Acids. Evidence that the Dog is Not a Relevant Species for Evaluation of Human Health Risk.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Timchalk, Chuck

    Phenoxyacetic acids including 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2-methylphenoxyacetic acid (MCPA) are widely utilized organic acid herbicides that have undergone extensive toxicity and pharmacokinetic analyses. The dog is particularly susceptible to the toxicity of phenoxyacetic acids and related organic acids relative to other species. Active renal clearance mechanisms for organic acids are ubiquitous in mammalian species, and thus a likely mechanism responsible for the increased sensitivity of the dog to these agents is linked to a lower capacity to secrete organic acids from the kidney. Using published data describing the pharmacokinetics of phenoxyacetic and structurally related organic acids in a varietymore » of species including humans, inter-species comparative pharmacokinetics were evaluated using allometic parameter scaling. For both 2,4-D and MCPA the dog plasma half-life (t1/2) and renal clearance (Clr; ml hr-1) rates did not scale as a function of body weight across species; whereas for all other species evaluated, including humans, these pharmacokinetic parameters reasonably scaled. This exceptional response in the dog is clearly illustrated by comparing the plasma t1/2 at comparable doses of 2,4-D and MCPA, across several species. At a dosage of 5 mg/kg, in dogs the plasma t1/2 for 2,4-D and MCPA were {approx}92 - 106 hr and 63 hr, respectively, which is substantially longer than in the rat ({approx}1 and 6 hr, respectively) or in humans (12 and 11 hr, respectively). This longer t1/2, and slower elimination in the dog, results in substantially higher body burdens of these organic acids, at comparable doses, relative to other species. Although these results indicate the important role of renal transport clearance mechanisms as determinants of the clearance and potential toxicity outcomes of phenoxyacetic acid herbicides across several species, other contributing mechanisms such as reabsorption from the renal tubules is highly

  12. Desialylation accelerates platelet clearance after refrigeration and initiates GPIbα metalloproteinase-mediated cleavage in mice

    PubMed Central

    Jansen, A. J. Gerard; Josefsson, Emma C.; Rumjantseva, Viktoria; Liu, Qiyong Peter; Falet, Hervé; Bergmeier, Wolfgang; Cifuni, Stephen M.; Sackstein, Robert; von Andrian, Ulrich H.; Wagner, Denisa D.; Hartwig, John H.

    2012-01-01

    When refrigerated platelets are rewarmed, they secrete active sialidases, including the lysosomal sialidase Neu1, and express surface Neu3 that remove sialic acid from platelet von Willebrand factor receptor (VWFR), specifically the GPIbα subunit. The recovery and circulation of refrigerated platelets is greatly improved by storage in the presence of inhibitors of sialidases. Desialylated VWFR is also a target for metalloproteinases (MPs), because GPIbα and GPV are cleaved from the surface of refrigerated platelets. Receptor shedding is inhibited by the MP inhibitor GM6001 and does not occur in Adam17ΔZn/ΔZn platelets expressing inactive ADAM17. Critically, desialylation in the absence of MP-mediated receptor shedding is sufficient to cause the rapid clearance of platelets from circulation. Desialylation of platelet VWFR therefore triggers platelet clearance and primes GPIbα and GPV for MP-dependent cleavage. PMID:22101895

  13. Serum hyaluronic acid in dogs with congenital portosystemic shunts.

    PubMed

    Seki, M; Asano, K; Sakai, M; Kanno, N; Teshima, K; Edamura, K; Tanaka, S

    2010-05-01

    To compare the serum level of hyaluronic acid in dogs with congenital portosystemic shunt with that in healthy dogs and to investigate the perioperative change in serum hyaluronic acid following shunt attenuation. Blood samples were obtained from 29 congenital portosystemic shunt dogs before the operation, and 2 and 4 weeks after the operation from 17 and 7 dogs, respectively. The serum hyaluronic acid level of these dogs was measured and compared with that of 10 healthy beagles. The median preoperative hyaluronic acid level in dogs with congenital portosystemic shunt was significantly elevated compared with that in healthy dogs. Furthermore, the median postoperative hyaluronic acid level significantly decreased compared with the median preoperative levels in congenital portosystemic shunt dogs. In the case of dogs with congenital portosystemic shunt, the reduction of intrahepatic portal blood flow might lower the clearance rate of hyaluronic acid in hepatic sinusoidal endothelial cells, so hyaluronic acid clearance could be improved by attenuation of a shunt vessel. Hence, serum hyaluronic acid levels might be useful to evaluate liver function and also have the potential to evaluate successful attenuation of a shunt vessel in dogs with congenital portosystemic shunt. Further investigations are required to clarify whether serum hyaluronic acid offers significant benefits over existing markers such as serum bile acid or ammonia concentrations.

  14. Online monitoring of dynamic tip clearance of turbine blades in high temperature environments

    NASA Astrophysics Data System (ADS)

    Han, Yu; Zhong, Chong; Zhu, Xiaoliang; Zhe, Jiang

    2018-04-01

    Minimized tip clearance reduces the gas leakage over turbine blade tips and improves the thrust and efficiency of turbomachinery. An accurate tip clearance sensor, measuring the dynamic clearances between blade tips and the turbine case, is a critical component for tip clearance control. This paper presents a robust inductive tip clearance sensor capable of monitoring dynamic tip clearances of turbine machines in high-temperature environments and at high rotational speeds. The sensor can also self-sense the temperature at a blade tip in situ such that temperature effect on tip clearance measurement can be estimated and compensated. To evaluate the sensor’s performance, the sensor was tested for measuring the tip clearances of turbine blades under various working temperatures ranging from 700 K to 1300 K and at turbine rotational speeds ranging from 3000 to 10 000 rpm. The blade tip clearance was varied from 50 to 2000 µm. The experiment results proved that the sensor can accurately measure the blade tip clearances with a temporal resolution of 10 µm. The capability of accurately measuring the tip clearances at high temperatures (~1300 K) and high turbine rotation speeds (~30 000 rpm), along with its compact size, makes it promising for online monitoring and active control of blade tip clearances of high-temperature turbomachinery.

  15. Numerical investigation of tip clearance effects on the performance of ducted propeller

    NASA Astrophysics Data System (ADS)

    Ding, Yongle; Song, Baowei; Wang, Peng

    2015-09-01

    Tip clearance loss is a limitation of the improvement of turbomachine performance. Previous studies show the Tip clearance loss is generated by the leakage flow through the tip clearance, and is roughly linearly proportional to the gap size. This study investigates the tip clearance effects on the performance of ducted propeller. The investigation was carried out by solving the Navier-Stokes equations with the commercial Computational Fluid Dynamic (CFD) code CFX14.5. These simulations were carried out to determine the underlying mechanisms of the tip clearance effects. The calculations were performed at three different chosen advance ratios. Simulation results showed that the tip loss slope was not linearly at high advance due to the reversed pressure at the leading edge. Three type of vortical structures were observed in the tip clearance at different clearance size.

  16. 32 CFR 644.517 - Clearance of Army lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Army lands. 644.517 Section 644.517 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal Clearance of Explosive Hazards and Other Contamination from Proposed Excess Land...

  17. Noncontact Capacitive Clearance Control System For Laser Cutting Machines

    NASA Astrophysics Data System (ADS)

    Topkaya, Ahmet; Schmall, Karl-Heinz; Majoli, Ralf

    1989-03-01

    For a continuous high quality laser cut, it is necessary among other things to position the focal point of the laser beam correctly. This means that a constant clearance between the cutting head and the workpiece with a tolerance of +/- 0.Imm must he ensured. When cutting corrugated automobile bodysheet for example, a good quality cut can only be achieved with automatic clearance control. In the following, a method of automatic clearance control is described using the assistance of a noncontact capacitive sensor system. The copper nozzle of the laser cutting head acts as the electrode of the clearance sensor. The nozzle electrode and the workpiece build a small variable capacitance depending on the clearance. A change of clearance also changes the capacitance, which in turn influences a high frequency oscillator circuit. This shift in frequency is then converted into an analogue DC signal, which can be used to operate a servo motor control for the positioning of the laser cutting head in a closed loop servo system. Laser cutting heads with clearance sensor nozzles of different shapes, suited fur most applications in the industry, with focal lengths from 2.5" to 5" have been developed. They are capable to cut metal sheet from 0.2 to 12 mm of thickness, using CO2-lasers with output power up to 2.5 kW. For special applications involving difficult workpiece topographies in automobile production applications special "trunk" nozzles have been developed. For 5-axis cutting machines and robots, new laser cutting heads with integrated nozzle sensors in combination with a high dynamic Z-axis motor drive are in a stage of development.

  18. Effects of semi-floating ring bearing outer clearance on the subsynchronous oscillation of turbocharger rotor

    NASA Astrophysics Data System (ADS)

    Liang, Feng; Zhou, Ming; Xu, Quanyong

    2016-09-01

    Semi-floating ring bearing(SFRB) is developed to control the vibration of turbocharger rotor. The outer clearance of SFRB affects the magnitude and frequency of nonlinear whirl motion, which is significant for the design of turbocharger. In order to explore the effects of outer clearance, a transient finite element analysis program for rotor and oil film bearing is built and validated by a published experimental case. The nonlinear dynamic behaviors of rotor-SFRB system are simulated. According to the simulation results, two representative subsynchronous oscillations excited by the two bearings respectively are discovered. As the outer clearance of SFRB increases from 24 μm to 60 μm, the low-frequency subsynchronous oscillation experiences three steps, including a strong start, a gradual recession and a combination with the other one. At the same time, the high-frequency subsynchronous oscillation starts to appear gradually, then strengthens, and finally combines. If gravity and unbalance are neglected, the combination will start starts from high rotor speed and extents to low rotor speed, just like a "zipper". It is found from the quantitative analysis that when the outer clearance increases, the vibration amplitude experiences large value firstly, then reduction, and suddenly increasing after combination. A useful design principle of SFRB outer clearance for minimum vibration amplitude is proposed: the outer clearance value should be chosen to keep the frequency of two subsynchronous oscillations clearly separated and their amplitudes close.

  19. New digital capacitive measurement system for blade clearances

    NASA Astrophysics Data System (ADS)

    Moenich, Marcel; Bailleul, Gilles

    This paper presents a totally new concept for tip blade clearance evaluation in turbine engines. This system is able to detect exact 'measurands' even under high temperature and severe conditions like ionization. The system is based on a heavy duty probe head, a miniaturized thick-film hybrid electronic circuit and a signal processing unit for real time computing. The high frequency individual measurement values are digitally filtered and linearized in real time. The electronic is built in hybrid technology and therefore can be kept extremely small and robust, so that the system can be used on actual flights.

  20. Benefits of Improved HP Turbine Active Clearance Control

    NASA Technical Reports Server (NTRS)

    Ruiz, Rafael; Albers, Bob; Sak, Wojciech; Seitzer, Ken; Steinetz, Bruce M.

    2007-01-01

    As part of the NASA Propulsion 21 program, GE Aircraft Engines was contracted to develop an improved high pressure turbine(HPT) active clearance control (ACC) system. The system is envisioned to minimize blade tip clearances to improve HPT efficiency throughout the engine operation range simultaneously reducing fuel consumption and emissions.

  1. Compressor blade clearance measurement using capacitance and phase lock techniques

    NASA Astrophysics Data System (ADS)

    Demers, Rosario N.

    1986-11-01

    The clearance measurement system has several unique features which mimimize problems plaguing earlier systems. These include tuning stability and sensitivity drift. Both these problems are intensified by the environmental factors present in compressors i.e., wide temperature fluctuations, vibrations, and conductive contamination of probe tips. The circuitry in this new system provides phase lock feedback to control tuning and shut calibration to measure sensitivity. The use of high frequency excitation lowers the probe tip impedance, thus miminizing the effects of contamination. A prototype has been built and tested. The ability to calibrate has been demonstrated. An eight channel system is now being constructed for use in the Compressor Research Facility at Wright-Patterson AFB. The efficiency of a turbine engine is to a large extent dependent upon the mechanical tolerances maintained between its moving parts. On critical tolerance is the blade span. Although this tolerance may not appear severe, the impact on compressor efficiency is dramatic. The penalty in percent efficiency has been shown to be three times the percent clearance to blade span ratio. In addition, each percent loss in compressor efficiency represents one half percent loss in specific fuel consumption. Factors which affect blade tip clearance are identified.

  2. Recent advances in capacitance type of blade tip clearance measurements

    NASA Technical Reports Server (NTRS)

    Barranger, John P.

    1988-01-01

    Two recent electronic advances at NASA-Lewis that meet the blade tip clearance needs of a wide class of fans, compressors, and turbines are described. The first is a frequency modulated (FM) oscillator that requires only a single low cost ultrahigh frequency operational amplifier. Its carrier frequency is 42.8 MHz when used with a 61 cm long hermetically sealed coaxial cable. The oscillator can be calibrated in the static mode and has a negative peak frequency deviation of 400 kHz for a typical rotor blade. High temperature performance tests of the probe and 13 cm of the adjacent cable show good accuracy up to 600 C, the maximum which produces a clearance error of + or - 10 microns at a clearance of 500 microns. In the second advance, a guarded probe configuration allows a longer cable capacitance. The capacitance of the probe is part of a small time constant feedback in a high speed operational amplifier. The solution of the governing differential equation is applied to a ramp type of input. The results show an amplifier output that contains a term which is proportional to the derivative of the feedback capacitance. The capacitance is obtained by subtracting a balancing reference channel followed by an integration stage.

  3. The detailed measurement of foot clearance by young adults during stair descent.

    PubMed

    Telonio, A; Blanchet, S; Maganaris, C N; Baltzopoulos, V; McFadyen, B J

    2013-04-26

    Foot clearance is an important variable for understanding safe stair negotiation, but few studies have provided detailed measures of it. This paper presents a new method to calculate minimal shoe clearance during stair descent and compares it to previous literature. Seventeen healthy young subjects descended a five step staircase with step treads of 300 mm and step heights of 188 mm. Kinematic data were collected with an Optotrak system (model 3020) and three non-colinear infrared markers on the feet. Ninety points were digitized on the foot sole prior to data collection using a 6 marker probe and related to the triad of markers on the foot. The foot sole was reconstructed using the Matlab (version 7.0) "meshgrid" function and minimal distance to each step edge was calculated for the heel, toe and foot sole. Results showed significant differences in minimum clearance between sole, heel and toe, with the shoe sole being the closest and the toe the furthest. While the hind foot sole was closest for 69% of the time, the actual minimum clearance point on the sole did vary across subjects and staircase steps. This new method, and the findings on healthy young subjects, can be applied to future studies of other populations and staircase dimensions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Delayed clearance of triglyceride‐rich lipoproteins in young, healthy obese subjects†

    PubMed Central

    Goll, R.; Lekahl, S.; Moen, O. S.; Florholmen, J.

    2015-01-01

    Summary Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age‐ and sex‐matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA‐IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA‐IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. PMID:26469529

  5. Plasmodium falciparum malaria: Convergent evolutionary trajectories towards delayed clearance following artemisinin treatment.

    PubMed

    Wilairat, Prapon; Kümpornsin, Krittikorn; Chookajorn, Thanat

    2016-05-01

    Malaria is a major global health challenge with 300million new cases every year. The most effective regimen for treating Plasmodium falciparum malaria is based on artemisinin and its derivatives. The drugs are highly effective, resulting in rapid clearance of parasites even in severe P. falciparum malaria patients. During the last five years, artemisinin-resistant parasites have begun to emerge first in Cambodia and now in Thailand and Myanmar. At present, the level of artemisinin resistance is relatively low with clinical presentation of delayed artemisinin clearance (a longer time to reduce parasite load) and a small decrease in artemisinin sensitivity in cultured isolates. Nevertheless, multiple genetic loci associated with delayed parasite clearance have been reported, but they cannot account for a large portion of cases. Even the most well-studied kelch 13 propeller mutations cannot always predict the outcome of artemisinin treatment in vitro and in vivo. Here we propose that delayed clearance by artemisinin could be the result of convergent evolution, driven by multiple trajectories to overcome artemisinin-induced stress, but precluded to become full blown resistance by high fitness cost. Genetic association studies by several genome-wide approaches reveal linkage disequilibrium between multiple loci and delayed parasite clearance. Genetic manipulations at some of these loci already have resulted in loss in artemisinin sensitivity. The notion presented here is by itself consistent with existing evidence on artemisinin resistance and has the potential to be explored using available genomic data. Most important of all, molecular surveillance of artemisinin resistance based on multi-genic markers could be more informative than relying on any one particular molecular marker. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Cleaning up the mess: cell corpse clearance in Caenorhabditis elegans.

    PubMed

    Pinto, Sérgio Morgado; Hengartner, Michael Otmar

    2012-12-01

    Genetic and cell biology studies have led to the identification in Caenorhabditis elegans of a set of evolutionary conserved cellular mechanisms responsible for the clearance of apoptotic cells. Based on the phenotype of cell corpse clearance mutants, corpse clearance can be divided into three distinct, but linked steps: corpse recognition, corpse internalization, and corpse degradation. Work in recent years has led to a better understanding of the molecular pathways that mediate each of these steps. Here, we review recent developments in our understanding of in vivo cell corpse clearance in this simple but most elegant model organism. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Apoptotic Cell Clearance in Development.

    PubMed

    Shklover, Jeny; Levy-Adam, Flonia; Kurant, Estee

    2015-01-01

    Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology. © 2015 Elsevier Inc. All rights reserved.

  8. Hawaii cohort study of serum micronutrient concentrations and clearance of incident oncogenic human papillomavirus infection of the cervix.

    PubMed

    Goodman, Marc T; Shvetsov, Yurii B; McDuffie, Katharine; Wilkens, Lynne R; Zhu, Xuemei; Franke, Adrian A; Bertram, Cathy Cramer; Kessel, Bruce; Bernice, Marge; Sunoo, Christian; Ning, Lily; Easa, David; Killeen, Jeffrey; Kamemoto, Lori; Hernandez, Brenda Y

    2007-06-15

    The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (clearance time was also significantly shorter among women with the highest compared with the lowest serum levels of alpha-tocopherol and total-tocopherol, but significant trends in these associations were limited to infections lasting Clearance of persistent HPV infection (lasting >120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.

  9. Four hour creatinine clearance is better than plasma creatinine for monitoring renal function in critically ill patients

    PubMed Central

    2012-01-01

    Introduction Acute kidney injury (AKI) diagnosis is based on an increase in plasma creatinine, which is a slowly changing surrogate of decreased glomerular filtration rate. We investigated whether serial creatinine clearance, a direct measure of the glomerular filtration rate, provided more timely and accurate information on renal function than serial plasma creatinine in critically ill patients. Methods Serial plasma creatinine and 4-hour creatinine clearance were measured 12-hourly for 24 hours and then daily in 484 patients. AKI was defined either as > 50% increase in plasma creatinine from baseline, or > 33.3% decrease in creatinine clearance. The diagnostic and predictive performance of the two AKI definitions were compared. Results Creatinine clearance decrease diagnosed AKI in 24% of those not diagnosed by plasma creatinine increase on entry. These patients entered the ICU sooner after insult than those diagnosed with AKI by plasma creatinine elevation (P = 0.0041). Mortality and dialysis requirement increased with the change in creatinine clearance-acute kidney injury severity class (P = 0.0021). Amongst patients with plasma creatinine < 1.24 mg/dl on entry, creatinine clearance improved the prediction of AKI considerably (Net Reclassification Improvement 83%, Integrated Discrimination Improvement 0.29). On-entry, creatinine clearance associated with AKI severity and duration (P < 0.0001) predicted dialysis need (area under the curve: 0.75) and death (0.61). A > 33.3% decrease in creatinine clearance over the first 12 hours was associated with a 2.0-fold increased relative risk of dialysis or death. Conclusions Repeated 4-hour creatinine clearance measurements in critically ill patients allow earlier detection of AKI, as well as progression and recovery compared to plasma creatinine. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN012606000032550. PMID:22713519

  10. A conceptual framework for dynamic extension of the red clearance interval as a countermeasure for red-light-running.

    PubMed

    Gates, Timothy J; Noyce, David A

    2016-11-01

    This manuscript describes the development and evaluation of a conceptual framework for real-time operation of dynamic on-demand extension of the red clearance interval as a countermeasure for red-light-running. The framework includes a decision process for determining, based on the real-time status of vehicles arriving at the intersection, when extension of the red clearance interval should occur and the duration of each extension. A zonal classification scheme was devised to assess whether an approaching vehicle requires additional time to safely clear the intersection based on the remaining phase time, type of vehicle, current speed, and current distance from the intersection. Expected performance of the conceptual framework was evaluated through modeling of replicated field operations using vehicular event data collected as part of this research. The results showed highly accurate classification of red-light-running vehicles needing additional clearance time and relatively few false extension calls from stopping vehicles, thereby minimizing the expected impacts to signal and traffic operations. Based on the recommended parameters, extension calls were predicted to occur once every 26.5cycles. Assuming a 90scycle, 1.5 extensions per hour were expected per approach, with an estimated extension time of 2.30s/h. Although field implementation was not performed, it is anticipated that long-term reductions in targeted red-light-running conflicts and crashes will likely occur if red clearance interval extension systems are implemented at locations where start-up delay on the conflicting approach is generally minimal, such as intersections with lag left-turn phasing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial.

    PubMed

    Nirmala, Svsg; Quadar, Mohammed Akhil; Veluru, Sindhuri

    2016-01-01

    Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate), filled (wafer and fruit and nuts chocolate), and candy (hard milk and mango-flavored candy) groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P < 0.05). Dark chocolate had a high fall in pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high.

  12. Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells.

    PubMed

    Li, Yun; Fu, Jianxin; Ling, Yun; Yago, Tadayuki; McDaniel, J Michael; Song, Jianhua; Bai, Xia; Kondo, Yuji; Qin, Yannan; Hoover, Christopher; McGee, Samuel; Shao, Bojing; Liu, Zhenghui; Sonon, Roberto; Azadi, Parastoo; Marth, Jamey D; McEver, Rodger P; Ruan, Changgeng; Xia, Lijun

    2017-08-01

    Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1 -/- ). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1 -/- mice show reduced levels of α-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets. The preferential accumulation of HC C1galt1 -/- platelets in the liver was reduced in mice lacking the hepatic asialoglycoprotein receptor [Ashwell-Morell receptor (AMR)]. However, we found that Kupffer cells are the primary cells phagocytosing HC C1galt1 -/- platelets in the liver. Our results demonstrate that hepatic AMR promotes preferential adherence to and phagocytosis of desialylated and/or HC C1galt1 -/- platelets by the Kupffer cell through its C-type lectin receptor CLEC4F. These findings provide insights into an essential role for core 1 O-glycosylation of platelets in their clearance in the liver.

  13. Postoperative ERCP versus laparoscopic choledochotomy for clearance of selected bile duct calculi: a randomized trial.

    PubMed

    Nathanson, Leslie K; O'Rourke, Nicholas A; Martin, Ian J; Fielding, George A; Cowen, Alistair E; Roberts, Roderick K; Kendall, Bradley J; Kerlin, Paul; Devereux, Benedict M

    2005-08-01

    alternative to sphincterotomy to allow stone extraction was not used. Major endpoints for the trial were operative time, morbidity, retained stone rate, reoperation rate, and hospital stay. From June 1998 to February 2003, 372 patients with BD stones had successful trans-cystic duct clearance of stones in 286, leaving 86 patients randomized into the trial. Total operative time was 10.9 minutes longer in the choledochotomy group (158.8 minutes), with slightly shorter hospital stay 6.4 days versus 7.7 days. Bile leak occurred in 14.6% of those having choledochotomy with similar rates of pancreatitis (7.3% versus 8.8%), retained stones (2.4% versus 4.4%), reoperation (7.3% versus 6.6%), and overall morbidity (17% versus 13%). These data suggest that the majority of secondary BD stones can be diagnosed at the time of cholecystectomy and cleared trans-cystically, with those failing having either choledochotomy or postoperative ERCP. However, because of the small trial size, a significant chance exists that small differences in outcome may exist. We would avoid choledochotomy in ducts less than 7 mm measured at the time of operative cholangiogram and severely inflamed friable tissues leading to a difficult dissection. We would advocate choledochotomy as a good choice for patients after Billroth 11 gastrectomy, failed ERCP access, or where long delays would occur for patient transfer to other locations for the ERCP.

  14. Gender and oral contraceptive steroids as determinants of drug glucuronidation: effects on clofibric acid elimination.

    PubMed Central

    Miners, J O; Robson, R A; Birkett, D J

    1984-01-01

    The disposition of clofibric acid, a drug metabolised largely by glucuronidation, was studied in eight males, eight females and eight females receiving oral contraceptive steroids (OCS). Clofibric acid plasma clearance was not significantly different in males compared to the control female group but was 48% greater (P less than 0.01) in women receiving OCS compared to non-pill using females. This difference was due to an alteration in clofibric acid metabolic clearance as there were no differences between the groups in clofibric acid free fraction. Along with previous data the results suggest that induction of drug glucuronidation by OCS may be of clinical importance, although any sex-related differences are unlikely to be of clinical significance. PMID:6487463

  15. The levonorgestrel-releasing intrauterine system is associated with delayed endocervical clearance of Chlamydia trachomatis without alterations in vaginal microbiota.

    PubMed

    Liechty, Emma R; Bergin, Ingrid L; Bassis, Christine M; Chai, Daniel; LeBar, William; Young, Vincent B; Bell, Jason D

    2015-11-01

    Progestin-based contraception may impact women's susceptibility to sexually transmitted infection. We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on cervical persistence of Chlamydia trachomatis (CT) in a baboon model. Female olive baboons (Papio anubis) with or without an LNG-IUS received CT or sham inoculations. CT was detected in cervical epithelium with weekly nucleic acid amplification testing (NAAT) and culture. Presence of the LNG-IUS was associated with prolonged persistence of CT. Median time to post-inoculation clearance of CT as detected by NAAT was 10 weeks (range 7-12) for animals with an LNG-IUS and 3 weeks (range 0-12) for non-LNG-IUS animals (P = 0.06). Similarly, median time to post-inoculation clearance of CT by culture was 9 weeks (range 3-12) for LNG-IUS animals and 1.5 weeks (range 0-10) for non-LNG-IUS animals (P = 0.04). We characterized the community structure of the vaginal microbiota with the presence of the LNG-IUS to determine if alterations in CT colonization dynamics were associated with changes in vaginal commensal bacteria. Vaginal swabs were collected weekly for microbiome analysis. Endocervical CT infection was not correlated with alterations in the vaginal microbiota. Together, these results suggest that LNG-IUS may facilitate CT endocervical persistence through a mechanism distinct from vaginal microbial alterations. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. 49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

  17. 49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

  18. 49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

  19. 49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

  20. 49 CFR 236.22 - Semaphore signal arm; clearance to other objects.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Semaphore signal arm; clearance to other objects... Rules and Instructions: All Systems Roadway Signals and Cab Signals § 236.22 Semaphore signal arm; clearance to other objects. At least one-half inch clearance shall be provided between semaphore signal arm...

  1. Gram-scale synthesis of coordination polymer nanodots with renal clearance properties for cancer theranostic applications

    NASA Astrophysics Data System (ADS)

    Liu, Fuyao; He, Xiuxia; Chen, Hongda; Zhang, Junping; Zhang, Huimao; Wang, Zhenxin

    2015-08-01

    An ultrasmall hydrodynamic diameter is a critical factor for the renal clearance of nanoparticles from the body within a reasonable timescale. However, the integration of diagnostic and therapeutic components into a single ultrasmall nanoparticle remains challenging. In this study, pH-activated nanodots (termed Fe-CPNDs) composed of coordination polymers were synthesized via a simple and scalable method based on coordination reactions among Fe3+, gallic acid and poly(vinylpyrrolidone) at ambient conditions. The Fe-CPNDs exhibited ultrasmall (5.3 nm) hydrodynamic diameters and electrically neutral surfaces. The Fe-CPNDs also exhibited pH-activatable magnetic resonance imaging contrast and outstanding photothermal performance. The features of Fe-CPNDs greatly increased the tumour-imaging sensitivity and facilitated renal clearance after injection in animal models in vivo. Magnetic resonance imaging-guided photothermal therapy using Fe-CPNDs completely suppressed tumour growth. These findings demonstrate that Fe-CPNDs constitute a new class of renal clearable nanomedicine for photothermal therapy and molecular imaging.

  2. Effect of amiloride and saline on nasal mucociliary clearance and potential difference in cystic fibrosis and normal subjects.

    PubMed Central

    Middleton, P. G.; Geddes, D. M.; Alton, E. W.

    1993-01-01

    BACKGROUND--Mucociliary clearance is an important component of pulmonary defence. Maximum clearance is thought to depend on an optimal depth of the sol layer, allowing the most efficient interaction between the cilia and the overlying mucus layer. Sodium absorption, the major ion transport in human airways, is thought to be important in the regulation of the depth of the sol layer. In the airways of patients with cystic fibrosis sodium absorption is increased and mucociliary clearance decreased. Amiloride, a sodium channel blocker, has been shown to improve pulmonary mucociliary clearance in patients with cystic fibrosis. However, its effects on nasal mucociliary clearance in either normal subjects or those with cystic fibrosis are unknown. A study was therefore performed to investigate whether nebulised amiloride improves nasal mucociliary clearance in normal or cystic fibrosis subjects. METHODS--Nasal mucociliary clearance was measured by the saccharin clearance technique in 12 normal subjects and 12 with cystic fibrosis. For the control study measurements were made on two consecutive days and the mean time for each subject averaged. For the drug study measurements were also made on two consecutive days, after administration of nasally nebulised amiloride or placebo (saline) in a double blind manner. Nasal potential difference was measured in eight patients with cystic fibrosis after the administration of amiloride or placebo to assess the efficacy of deposition and duration of action. RESULTS--Baseline values of mucociliary clearance were significantly faster in the normal subjects than in those with cystic fibrosis. In both groups mucociliary clearance was increased after both saline and amiloride, with no significant difference between either treatment. As previously reported, baseline nasal potential difference was significantly more negative in the subjects with cystic fibrosis. Amiloride significantly reduced the potential difference for at least 60 minutes

  3. Estimation of end point foot clearance points from inertial sensor data.

    PubMed

    Santhiranayagam, Braveena K; Lai, Daniel T H; Begg, Rezaul K; Palaniswami, Marimuthu

    2011-01-01

    Foot clearance parameters provide useful insight into tripping risks during walking. This paper proposes a technique for the estimate of key foot clearance parameters using inertial sensor (accelerometers and gyroscopes) data. Fifteen features were extracted from raw inertial sensor measurements, and a regression model was used to estimate two key foot clearance parameters: First maximum vertical clearance (m x 1) after toe-off and the Minimum Toe Clearance (MTC) of the swing foot. Comparisons are made against measurements obtained using an optoelectronic motion capture system (Optotrak), at 4 different walking speeds. General Regression Neural Networks (GRNN) were used to estimate the desired parameters from the sensor features. Eight subjects foot clearance data were examined and a Leave-one-subject-out (LOSO) method was used to select the best model. The best average Root Mean Square Errors (RMSE) across all subjects obtained using all sensor features at the maximum speed for m x 1 was 5.32 mm and for MTC was 4.04 mm. Further application of a hill-climbing feature selection technique resulted in 0.54-21.93% improvement in RMSE and required fewer input features. The results demonstrated that using raw inertial sensor data with regression models and feature selection could accurately estimate key foot clearance parameters.

  4. Integrated viral clearance strategies-reflecting on the present, projecting to the future.

    PubMed

    Roush, David J

    2018-01-20

    Viral clearance and inactivation are critical steps in ensuring the safety of biological products derived from mammalian cell culture and are a component of an adventitious agent control strategy which spans both upstream and downstream processes. Although these approaches have been sufficient to support the development of biologics to date, the empirical and semi-quantitative nature of the approach leaves some potential gaps. For example, the concept of performing a quantitative risk assessment for the downstream components of virus safety was introduced in ICH Q5A for XMuLV. An ideal future state would be to perform a similar quantitative risk assessment for a range of viruses based on an assessment of potential virus risk in both upstream and downstream processes. This assessment combined with an integrated control strategy (including monitoring) would be extremely beneficial in minimizing potential adventitious agent risks. Significant progress has been achieved towards this goal in the last several years including recent advances in quantification of virus sequences in cell banks (ADVTIG), development of truly modular or generic viral clearance claims for specific unit operations, enhanced controls of upstream media (HTST/nanofiltration) and the use of RVLP for in-process monitoring. The recent shift towards continuous processing has the potential to enhance the criticality of in-line monitoring and the complexity of viral clearance and inactivation (owing to a wide range of potential 'worst case' viral clearance scenarios). However, gaps exist in, firstly, the ability to quantify potential virus risk levels in process streams in real-time, secondly, mechanistic understanding of virus/chromatography media interactions, and thirdly, mechanistic understanding of virus/filter interactions. Some new technologies may also need to be developed to allow for real-time confirmation of virus inactivation and clearance to support process development (both batch and

  5. The Role of Radial Clearance on the Performance of Foil Air Bearings

    NASA Technical Reports Server (NTRS)

    Radil, Kevin; Howard, Samuel; Dykas, Brian

    2002-01-01

    Load capacity tests were conducted to determine how radial clearance variations affect the load capacity coefficient of foil air bearings. Two Generation III foil air bearings with the same design but possessing different initial radial clearances were tested at room temperature against an as-ground PS304 coated journal operating at 30,000 rpm. Increases in radial clearance were accomplished by reducing the journal's outside diameter via an in-place grinding system. From each load capacity test the bearing load capacity coefficient was calculated from the rule-of-thumb (ROT) model developed for foil air bearings. The test results indicate that, in terms of the load capacity coefficient, radial clearance has a direct impact on the performance of the foil air bearing. Each test bearing exhibited an optimum radial clearance that resulted in a maximum load capacity coefficient. Relative to this optimum value are two separate operating regimes that are governed by different modes of failure. Bearings operating with radial clearances less than the optimum exhibit load capacity coefficients that are a strong function of radial clearance and are prone to a thermal runaway failure mechanism and bearing seizure. Conversely, a bearing operating with a radial clearance twice the optimum suffered only a 20 percent decline in its maximum load capacity coefficient and did not experience any thermal management problems. However, it is unknown to what degree these changes in radial clearance had on other performance parameters, such as the stiffness and damping properties of the bearings.

  6. Human-in-the-Loop Assessment of Alternative Clearances in Interval Management Arrival Operations

    NASA Technical Reports Server (NTRS)

    Baxley, Brian T.; Wilson, Sara R.; Swieringa, Kurt A.; Johnson, William C.; Roper, Roy D.; Hubbs, Clay E.; Goess, Paul A.; Shay, Richard F.

    2016-01-01

    Interval Management Alternative Clearances (IMAC) was a human-in-the-loop simulation experiment conducted to explore the Air Traffic Management (ATM) Technology Demonstration (ATD-1) Concept of Operations (ConOps), which combines advanced arrival scheduling, controller decision support tools, and aircraft avionics to enable multiple time deconflicted, efficient arrival streams into a high-density terminal airspace. Interval Management (IM) is designed to support the ATD-1 concept by having an "Ownship" (IM-capable) aircraft achieve or maintain a specific time or distance behind a "Target" (preceding) aircraft. The IM software uses IM clearance information and the Ownship data (route of flight, current location, and wind) entered by the flight crew, and the Target aircraft's Automatic Dependent Surveillance-Broadcast state data, to calculate the airspeed necessary for the IM-equipped aircraft to achieve or maintain the assigned spacing goal.

  7. Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model.

    PubMed

    Rygg, Alex; Longest, P Worth

    2016-10-01

    The objective of this study was to develop a computational fluid dynamics (CFD) model to predict the deposition, dissolution, clearance, and absorption of pharmaceutical particles in the human nasal cavity. A three-dimensional nasal cavity geometry was converted to a surface-based model, providing an anatomically-accurate domain for the simulations. Particle deposition data from a commercial nasal spray product was mapped onto the surface model, and a mucus velocity field was calculated and validated with in vivo nasal clearance rates. A submodel for the dissolution of deposited particles was developed and validated based on comparisons to existing in vitro data for multiple pharmaceutical products. A parametric study was then performed to assess sensitivity of epithelial drug uptake to model conditions and assumptions. The particle displacement distance (depth) in the mucus layer had a modest effect on overall drug absorption, while the mucociliary clearance rate was found to be primarily responsible for drug uptake over the timescale of nasal clearance for the corticosteroid mometasone furoate (MF). The model revealed that drug deposition in the nasal vestibule (NV) could slowly be transported into the main passage (MP) and then absorbed through connection of the liquid layer in the NV and MP regions. As a result, high intersubject variability in cumulative uptake was predicted, depending on the length of time the NV dose was left undisturbed without blowing or wiping the nose. This study has developed, for the first time, a complete CFD model of nasal aerosol delivery from the point of spray formation through absorption at the respiratory epithelial surface. For the development and assessment of nasal aerosol products, this CFD-based in silico model provides a new option to complement existing in vitro nasal cast studies of deposition and in vivo imaging experiments of clearance.

  8. Axial compressor blade design for desensitization of aerodynamic performance and stability to tip clearance

    NASA Astrophysics Data System (ADS)

    Erler, Engin

    region, this approach would entail a nominal performance penalty. Therefore, the chosen rotor design philosophy aims to keep the spanwise loading constant to avoid trading performance for desensitization. The rotor designs that resulted from this exercise are simulated in ANSYS CFX at different tip clearance sizes. The change in their performance with respect to tip clearance size (sensitivity) is compared both on an integral level in terms of pressure ratio and adiabatic efficiency, as well as on a detailed level in terms of aerodynamic losses and blockage associated with tip clearance flow. The sensitivity of aerodynamic stability is evaluated either directly through the simulations of the rotor characteristics up to the stall point (expensive in time and resources) for a few designs or indirectly through the position of the interface between the incoming and tip clearance flow with respect to the rotor leading edge plane. The latter approach is based on a generally observed stall criteria in modern axial compressors. The rotor designs are then assessed according to their sensitivity in comparison to that of the reference rotor design to detect features that can explain the trend in sensitivity to tip clearance size. These features can then be validated and the associated flow mechanisms explained through numerical simulations and modelling. Analysis of the database from the rotor parametric study shows that the observed trend in sensitivity cannot be explained by the shifting of the aerodynamic loading along the blade chord, as initially hypothesized based on the literature review. Instead, two flow features are found to reduce sensitivity of performance and stability to tip clearance, namely an increase in incoming meridional momentum in the tip region and a reduction/elimination of double leakage flow. Double leakage flow is the flow that exits the tip clearance of one blade and proceeds into the clearance of the adjacent blade rather than convecting downstream out

  9. A Parametric Study of Actuator Requirements for Active Turbine Tip Clearance Control of a Modern High Bypass Turbofan Engine

    NASA Technical Reports Server (NTRS)

    Kratz, Jonathan L.; Chapman, Jeffryes W.; Guo, Ten-Huei

    2017-01-01

    The efficiency of aircraft gas turbine engines is sensitive to the distance between the tips of its turbine blades and its shroud, which serves as its containment structure. Maintaining tighter clearance between these components has been shown to increase turbine efficiency, increase fuel efficiency, and reduce the turbine inlet temperature, and this correlates to a longer time-on-wing for the engine. Therefore, there is a desire to maintain a tight clearance in the turbine, which requires fast response active clearance control. Fast response active tip clearance control will require an actuator to modify the physical or effective tip clearance in the turbine. This paper evaluates the requirements of a generic active turbine tip clearance actuator for a modern commercial aircraft engine using the Commercial Modular Aero-Propulsion System Simulation 40k (C-MAPSS40k) software that has previously been integrated with a dynamic tip clearance model. A parametric study was performed in an attempt to evaluate requirements for control actuators in terms of bandwidth, rate limits, saturation limits, and deadband. Constraints on the weight of the actuation system and some considerations as to the force which the actuator must be capable of exerting and maintaining are also investigated. From the results, the relevant range of the evaluated actuator parameters can be extracted. Some additional discussion is provided on the challenges posed by the tip clearance control problem and the implications for future small core aircraft engines.

  10. Ramp-integration technique for capacitance-type blade-tip clearance measurement

    NASA Astrophysics Data System (ADS)

    Sarma, Garimella R.; Barranger, John P.

    The analysis of a proposed new technique for capacitance type blade tip clearance measurement is presented. The capacitance between the blade tip and a mounted capacitance electrode within a guard ring forms one of the feedback elements of a high speed operational amplifier. The differential equation governing the operational amplifier circuit is formulated and solved for two types of inputs to the amplifier - a constant voltage and a ramp. The resultant solution shows an output that contains a term that is proportional to the derivative of the product of the input voltage and the time constant of the feedback network. The blade tip clearance capacitance is obtained by subtracting the output of a balancing reference channel followed by integration. The proposed sampled data algorithm corrects for environmental effects and varying rotor speeds on-line, making the system suitable for turbine instrumentation. System requirements, block diagrams, and a typical application are included.

  11. Ramp-integration technique for capacitance-type blade-tip clearance measurement

    NASA Astrophysics Data System (ADS)

    Sarma, G. R.; Barranger, J. P.

    1986-05-01

    The analysis of a proposed new technique for capacitance type blade tip clearance measurement is presented. The capacitance between the blade tip and a mounted capacitance electrode within a guard ring forms one of the feedback elements of a high speed operational amplifier. The differential equation governing the operational amplifier circuit is formulated and solved for two types of inputs to the amplifier - a constant voltage and a ramp. The resultant solutions shows an output that contains a term that is proportional to the derivative of the product of the input voltage and the time constant of the feedback network. The blade tip clearance capacitance is obtained by subtracting the output of a balancing reference channel followed by integration. The proposed sampled data algorithm corrects the environmental effects and varying rotor speeds on-line, making the system suitable for turbine instrumentation. System requirements, block diagrams, and typical application are included.

  12. Ramp-integration technique for capacitance-type blade-tip clearance measurement

    NASA Technical Reports Server (NTRS)

    Sarma, Garimella R.; Barranger, John P.

    1986-01-01

    The analysis of a proposed new technique for capacitance type blade tip clearance measurement is presented. The capacitance between the blade tip and a mounted capacitance electrode within a guard ring forms one of the feedback elements of a high speed operational amplifier. The differential equation governing the operational amplifier circuit is formulated and solved for two types of inputs to the amplifier - a constant voltage and a ramp. The resultant solution shows an output that contains a term that is proportional to the derivative of the product of the input voltage and the time constant of the feedback network. The blade tip clearance capacitance is obtained by subtracting the output of a balancing reference channel followed by integration. The proposed sampled data algorithm corrects for environmental effects and varying rotor speeds on-line, making the system suitable for turbine instrumentation. System requirements, block diagrams, and a typical application are included.

  13. Ramp-integration technique for capacitance-type blade-tip clearance measurement

    NASA Technical Reports Server (NTRS)

    Sarma, G. R.; Barranger, J. P.

    1986-01-01

    The analysis of a proposed new technique for capacitance type blade tip clearance measurement is presented. The capacitance between the blade tip and a mounted capacitance electrode within a guard ring forms one of the feedback elements of a high speed operational amplifier. The differential equation governing the operational amplifier circuit is formulated and solved for two types of inputs to the amplifier - a constant voltage and a ramp. The resultant solutions shows an output that contains a term that is proportional to the derivative of the product of the input voltage and the time constant of the feedback network. The blade tip clearance capacitance is obtained by subtracting the output of a balancing reference channel followed by integration. The proposed sampled data algorithm corrects the environmental effects and varying rotor speeds on-line, making the system suitable for turbine instrumentation. System requirements, block diagrams, and typical application are included.

  14. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

  15. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

  16. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

  17. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

  18. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

  19. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

  20. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking the...

  1. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance office...

  2. HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal

    PubMed Central

    Wu, Guoxin; Swanson, Michael; Talla, Aarthi; Graham, Donald; Strizki, Julie; Gorman, Daniel; Barnard, Richard J.O.; Blair, Wade; Søgaard, Ole S.; Tolstrup, Martin; Østergaard, Lars; Rasmussen, Thomas A.; Sekaly, Rafick-Pierre; Archin, Nancie M.; Hazuda, Daria J.; Howell, Bonnie J.

    2017-01-01

    Promising therapeutic approaches for eradicating HIV include transcriptional activation of provirus from latently infected cells using latency-reversing agents (LRAs) and immune-mediated clearance to purge reservoirs. Accurate detection of cells capable of producing viral antigens and virions, and the measurement of clearance of infected cells, is essential to assessing therapeutic efficacy. Here, we apply enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4+ T cells from ART-suppressed HIV+ individuals, and we show viral protein induction following treatment with LRAs. Importantly, we demonstrate that clinical administration of histone deacetylase inhibitors (HDACis; vorinostat and panobinostat) induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. These findings extend beyond classical nucleic acid endpoints, which are confounded by the predominance of mutated, defective proviruses and, of paramount importance, enable assessment of cells making HIV protein that can now be targeted by immunological approaches. PMID:28814661

  3. Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

    PubMed

    Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

    2017-02-01

    Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4th hour of PET as slow transporter (< 0.47), slow-average transporter (0.47 - 0.56), fast-average transporter (0.57 - 0.67), and fast transporter (> 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p < 0.001) and therefore higher peritoneal phosphorus clearance (61.7 ± 15.1 L/week/1.73 m2 vs. 48.4 ± 14.0 L/week/1.73 m2, p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
.

  4. Increasing the Air Charge and Scavenging the Clearance Volume of a Compression-Ignition Engine

    NASA Technical Reports Server (NTRS)

    Spanogle, J A; Hicks, C W; Foster, H H

    1934-01-01

    The object of the investigation presented in this report was to determine the effects of increasing the air charge and scavenging the clearance volume of a 4-stroke-cycle compression-ignition engine having a vertical-disk form combustion chamber. Boosting the inlet-air pressure with normal valve timing increased the indicated engine power in proportion to the additional air inducted and resulted in smoother engine operation with less combustion shock. Scavenging the clearance volume by using a valve overlap of 145 degrees and an inlet-air boost pressure of approximately 2 1/2 inches of mercury produced a net increase in performance for clear exhaust operation of 33 percent over that obtained with normal valve timing and the same boost pressure. The improved combustion characteristics result in lower specific fuel consumption, and a clearer exhaust.

  5. Underkeel Clearance Study.

    DTIC Science & Technology

    1981-09-01

    EnterewJ N00014-80-C-0395 CONTENTS Page EXECUTIVE SUMMARY 1.0 INTRODUCTION 1.1 The Underlying Problem ................. 1-1 1.2 The Current Study...3-4 3.2.4 CVN Berthinq Facilities .................... 3-4 ii! JI N00014-80-C-0395 CONTENTS (continued) 3.3 Hydrologic Conditions...Drafts ...................... 3-10 3.8.3 Underkeel Clearance ........ .............. 3-10 4.0 THE ANALYSIS 4.1 The Physical Model

  6. No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

    PubMed Central

    Maiga, Amelia W.; Fofana, Bakary; Sagara, Issaka; Dembele, Demba; Dara, Antoine; Traore, Oumar Bila; Toure, Sekou; Sanogo, Kassim; Dama, Souleymane; Sidibe, Bakary; Kone, Aminatou; Thera, Mahamadou A.; Plowe, Christopher V.; Doumbo, Ogobara K.; Djimde, Abdoulaye A.

    2012-01-01

    Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa. PMID:22764287

  7. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

  8. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

  9. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

  10. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to taking...

  11. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling.

    PubMed

    Qosa, Hisham; Abuasal, Bilal S; Romero, Ignacio A; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N; Kaddoumi, Amal

    2014-04-01

    Alzheimer's disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected (125)I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of (125)I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of (125)I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in (125)I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes

  12. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: Kinetic analysis and mechanistic modeling

    PubMed Central

    Qosa, Hisham; Abuasal, Bilal S.; Romero, Ignacio A.; Weksler, Babette; Couraud, Pierre-Oliver; Keller, Jeffrey N.; Kaddoumi, Amal

    2014-01-01

    Alzheimer’s disease (AD) has a characteristic hallmark of amyloid-β (Aβ) accumulation in the brain. This accumulation of Aβ has been related to its faulty cerebral clearance. Indeed, preclinical studies that used mice to investigate Aβ clearance showed that efflux across blood-brain barrier (BBB) and brain degradation mediate efficient Aβ clearance. However, the contribution of each process to Aβ clearance remains unclear. Moreover, it is still uncertain how species differences between mouse and human could affect Aβ clearance. Here, a modified form of the brain efflux index method was used to estimate the contribution of BBB and brain degradation to Aβ clearance from the brain of wild type mice. We estimated that 62% of intracerebrally injected 125I-Aβ40 is cleared across BBB while 38% is cleared by brain degradation. Furthermore, in vitro and in silico studies were performed to compare Aβ clearance between mouse and human BBB models. Kinetic studies for Aβ40 disposition in bEnd3 and hCMEC/D3 cells, representative in vitro mouse and human BBB models, respectively, demonstrated 30-fold higher rate of 125I-Aβ40 uptake and 15-fold higher rate of degradation by bEnd3 compared to hCMEC/D3 cells. Expression studies showed both cells to express different levels of P-glycoprotein and RAGE, while LRP1 levels were comparable. Finally, we established a mechanistic model, which could successfully predict cellular levels of 125I-Aβ40 and the rate of each process. Established mechanistic model suggested significantly higher rates of Aβ uptake and degradation in bEnd3 cells as rationale for the observed differences in 125I-Aβ40 disposition between mouse and human BBB models. In conclusion, current study demonstrates the important role of BBB in the clearance of Aβ from the brain. Moreover, it provides insight into the differences between mouse and human BBB with regards to Aβ clearance and offer, for the first time, a mathematical model that describes A

  13. Tear clearance implications for ocular surface health.

    PubMed

    de Paiva, Cintia Sade; Pflugfelder, Stephen C

    2004-03-01

    Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

  14. CF6 Jet Engine Diagnostics Program: High pressure compressor clearance investigation

    NASA Technical Reports Server (NTRS)

    Radomski, M. A.

    1982-01-01

    The effects of high pressure compressor clearance changes on engine performance were experimentally determined on a CF6 core engine. The results indicate that a one percent reduction in normalized average clearance, expressed as a fraction of airfoil length, improves compressor efficiency by one percent. Compressor clearances are reduced by the application of rotor bore cooling, insulation of the stator casing, and use of a low coefficient of expansion material in the aft stages. This improvement amounts to a reduction of normalized average clearance of 0.78 percent, relative to CF6-60 compressor, which is equivalent to an improvement in compressor efficiency of 0.78 percent.

  15. Clearance of polonium-210-enriched cigarette smoke from the rat trachea and lung.

    PubMed

    Cohen, B S; Harley, N H; Tso, T C

    1985-06-30

    The distribution and clearance of alpha radioactivity in the lungs of rats were measured after inhalation of smoke from cigarettes highly enriched in 210Po. Female Fischer rats were exposed daily for 6 months to smoke from cigarettes with 500 times the normal content of 210Po. Control rats were exposed to standard cigarette smoke. Animals were serially withdrawn and killed. After necropsy the trachea, major bronchi, larynx, and nasopharynx were examined for surface alpha activity by an etched track technique utilizing cellulose nitrate detectors. Areas of accumulated activity were seen on samples of larynx from rats exposed to the 210Po-enriched cigarettes. No other local accumulations were seen on the airways. The lower lungs were analyzed radiochemically for 210Po. Both radiochemical analysis and track measurements showed highly elevated activity concentrations in rats exposed to the 210Po-enriched cigarettes. Following withdrawal from smoking, both short- and long-term clearance components were seen. The parameters which fit the postexposure data for clearance of the lung burden cannot fit the buildup during the exposure period.

  16. Toward a Fast-Response Active Turbine Tip Clearance Control

    NASA Technical Reports Server (NTRS)

    Melcher, Kevin J.; Kypuros, Javier A.

    2003-01-01

    This paper describes active tip clearance control research being conducted by NASA to improve turbine engine systems. The target application for this effort is commercial aircraft engines. However, technologies developed for clearance control can benefit a broad spectrum of current and future turbomachinery. The first portion of the paper addresses the research from a programmatic viewpoint. Recent studies that provide motivation for the work, identification of key technologies, and NASA's plan for addressing deficiencies in the technologies are discussed. The later portion of the paper drills down into one of the key technologies by presenting equations and results for a preliminary dynamic model of the tip clearance phenomena.

  17. Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

    PubMed

    Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

    1992-04-01

    Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

  18. 78 FR 5780 - Agency Information Collection Activities: Proposed Collection, Comment Request: Generic Clearance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... could change significantly based on the collection method ultimately used in the research. Estimated..., Comment Request: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... qualitative consumer and stakeholder feedback in an efficient, timely manner to facilitate service delivery...

  19. 49 CFR 392.12 - Highway-rail crossings; safe clearance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Highway-rail crossings; safe clearance. 392.12... DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.12 Highway-rail crossings; safe clearance. No driver of a commercial motor vehicle shall drive onto a highway-rail grade crossing...

  20. 49 CFR 392.12 - Highway-rail crossings; safe clearance.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Highway-rail crossings; safe clearance. 392.12... DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.12 Highway-rail crossings; safe clearance. No driver of a commercial motor vehicle shall drive onto a highway-rail grade crossing...

  1. 76 FR 17615 - Highway-Rail Grade Crossing; Safe Clearance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-30

    ...-2006-25660] RIN 2137-AE69 & 2126-AB04 Highway-Rail Grade Crossing; Safe Clearance AGENCY: Pipeline and... PHMSA and FMCSA extend the comment period for the Highway-Rail Grade Crossing; Safe Clearance Notice of... Alliance (CVSA) requested that PHMSA and FMCSA extend the comment period for the Highway-Rail Grade...

  2. 48 CFR 832.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 832.502-2 Contract finance office clearance. Contracting...

  3. 48 CFR 32.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 32.502-2 Contract finance office clearance. The contracting...

  4. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

  5. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

  6. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 27.411 Section 27.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

  7. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Ground clearance: tail rotor guard. 29.411 Section 29.411 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to...

  8. An on-line calibration technique for improved blade by blade tip clearance measurement

    NASA Astrophysics Data System (ADS)

    Sheard, A. G.; Westerman, G. C.; Killeen, B.

    A description of a capacitance-based tip clearance measurement system which integrates a novel technique for calibrating the capacitance probe in situ is presented. The on-line calibration system allows the capacitance probe to be calibrated immediately prior to use, providing substantial operational advantages and maximizing measurement accuracy. The possible error sources when it is used in service are considered, and laboratory studies of performance to ascertain their magnitude are discussed. The 1.2-mm diameter FM capacitance probe is demonstrated to be insensitive to variations in blade tip thickness from 1.25 to 1.45 mm. Over typical compressor blading the probe's range was four times the variation in blade to blade clearance encountered in engine run components.

  9. Quantitative analysis of myocardial kinetics of 15-p-[iodine-125] iodophenylpentadecanoic acid.

    PubMed

    DeGrado, T R; Holden, J E; Ng, C K; Raffel, D M; Gatley, S J

    1989-07-01

    Myocardial extraction and the characteristic tissue clearance of radioactivity following bolus injections of a radioiodinated (125I) long chain fatty acid (LCFA) analog 15-p-iodophenylpentadecanoic acid (IPPA) were examined in the isolated perfused working rat heart. Radioactivity remaining in the heart was monitored with external scintillation probes. A compartmental model which included nonesterified tracer, catabolite, and complex lipid compartments successfully fitted tissue time-radioactivity residue curves, and gave a value for the rate of IPPA oxidation 1.8 times that obtained from steady-state release of tritiated water from labeled palmitic acid. The technique was sensitive to the impairment of LCFA oxidation in hearts of animals treated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). IPPA or similar modified fatty acids may be better than 11C-labeled physiological fatty acids such as palmitate in this type of study, because efflux of unoxidized tracer and catabolite(s) from the heart are kinetically more distinct, and their contributions to the early data can be reliably separated. This technique may be suitable for extension to in vivo measurements with position tomography and appropriate modified fatty acids.

  10. Comparison of Two Alternate Methods for Tracking Toe Clearance

    NASA Technical Reports Server (NTRS)

    Miller, Christopher A.; Feiveson, Alan H.; Bloomberg, Jacob J.

    2007-01-01

    Analyses of toe clearance during the swing phase of locomotion has often been utilized in determining a subject s propensity to trip while either walking or stepping over an obstacle. In the literature, toe clearance has been studied using a marker on the superior aspect of the second toe (rtoe), a marker on the lateral aspect of the fifth metatarsal head (mth5), or a virtual marker positioned at the anterior tip of the toe (vtoe). The purpose of this study was to compute toe clearance and associated parameters using a fifth metatarsal marker and a virtual toe marker, and compare the results with those of the standard toe marker. Subjects walked on a motorized treadmill at five different speeds while performing a visual acuity task at two separate target distances (ten 60-second trials). The minimum vertical height (TCl) was determined for each stride, along with its point of occurence in the gait cycle, and the angles of the foot and ankle at that time. A regression analysis was performed on the vtoe and mth5 results versus rtoe individually. For all TCl parameters, the mth5 marker did not correlate well with rtoe; the vtoe marker showed better agreement. Most importantly, the mth5 marker predicted a later occurence of TCl than rtoe and vtoe - thereby missing the most dangerous point in swing phase for a trip. From this analysis, the vtoe marker proved to be a better analog to rtoe than mth5, especially for determining a subject s propensity to trip.

  11. 32 CFR 644.516 - Clearance of Air Force lands.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Air Force lands. 644.516 Section 644... Excess Land and Improvements § 644.516 Clearance of Air Force lands. The Chief of Engineers has no responsibility for inspecting or clearing excess Air Force land of explosives or chemical/biological contaminants...

  12. 48 CFR 1432.502-2 - Contract finance office clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL CONTRACTING REQUIREMENTS CONTRACT FINANCING Progress Payments Based on Costs 1432.502-2 Contract finance office clearance. The CO shall...

  13. 31 CFR 205.20 - What is a clearance pattern?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., unless additional data is required to accurately represent the flow of Federal funds. (e) If a State uses... FEDERAL-STATE FUNDS TRANSFERS Rules Applicable to Federal Assistance Programs Included in a Treasury-State Agreement § 205.20 What is a clearance pattern? States use clearance patterns to project when funds are paid...

  14. Domiciliary humidification improves lung mucociliary clearance in patients with bronchiectasis.

    PubMed

    Hasani, A; Chapman, T H; McCool, D; Smith, R E; Dilworth, J P; Agnew, J E

    2008-01-01

    Inspired air humidification has been reported to show some benefit in bronchiectatic patients. We have investigated the possibility that one effect might be to enhance mucociliary clearance. Such enhancement might, if it occurs, help to lessen the risks of recurrent infective episodes. Using a radioaerosol technique, we measured lung mucociliary clearance before and after 7 days of domiciliary humidification. Patients inhaled high flow saturated air at 37 degrees C via a patient-operated humidification nasal inhalation system for 3 h per day. We assessed tracheobronchial mucociliary clearance from the retention of (99m)Tc-labelled polystyrene tracer particles monitored for 6 h, with a follow-up 24-h reading. Ten out of 14 initially recruited patients (age 37-75 years; seven females) completed the study (two withdrew after their initial screening and two prior to the initial clearance test). Seven patients studied were non-smokers; three were ex-smokers (1-9 pack-years). Initial tracer radioaerosol distribution was closely similar between pre- and post-treatment. Following humidification, lung mucociliary clearance significantly improved, the area under the tracheobronchial retention curve decreased from 319 +/- 50 to 271 +/- 46%h (p < 0.07). Warm air humidification treatment improved lung mucociliary clearance in our bronchiectatic patients. Given this finding plus increasing laboratory and clinical interest in humidification mechanisms and effects, we believe further clinical trials of humidification therapy are desirable, coupled with analysis of humidification effects on mucus properties and transport.

  15. Rotating coherent flow structures as a source for narrowband tip clearance noise from axial fans

    NASA Astrophysics Data System (ADS)

    Zhu, Tao; Lallier-Daniels, Dominic; Sanjosé, Marlène; Moreau, Stéphane; Carolus, Thomas

    2018-03-01

    Noise from axial fans typically increases significantly as the tip clearance is increased. In addition to the broadband tip clearance noise at the design flow rate, narrowband humps also associated with the tip flow are observed in the far-field acoustic spectra at lower flow rate. In this study, both experimental and numerical methods are used to shed more light on the noise generation mechanism of this narrowband tip clearance noise and provide a unified description of this source. Unsteady aeroacoustic predictions with the Lattice-Boltzmann Method (LBM) are successfully compared with experiment. Such a validation allows using LBM data to conduct a detailed modal analysis of the pressure field for detecting rotating coherent flow structures which might be considered as noise sources. As previously found in ring fans the narrowband humps in the far-field noise spectra are found to be related to the tip clearance noise that is generated by an interaction of coherent flow structures present in the tip region with the leading edge of the impeller blades. The visualization of the coherent structures shows that they are indeed part of the unsteady tip clearance vortex structures. They are hidden in a complex, spatially and temporally inhomogeneous flow field, but can be recovered by means of appropriate filtering techniques. Their pressure trace corresponds to the so-called rotational instability identified in previous turbomachinery studies, which brings a unified picture of this tip-noise phenomenon for the first time.

  16. 48 CFR 245.7101-4 - DD Form 1640, Request for Plant Clearance.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false DD Form 1640, Request for Plant Clearance. 245.7101-4 Section 245.7101-4 Federal Acquisition Regulations System DEFENSE... Forms 245.7101-4 DD Form 1640, Request for Plant Clearance. Use to request plant clearance assistance or...

  17. Site clearance working group

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sitesmore » that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.« less

  18. Experimental basis of myocardial imaging with 123I-labeled hexadecenoic acid.

    PubMed

    Poe, N D; Robinson, G D; Graham, L S; MacDonald, N S

    1976-12-01

    Progress in myocardial perfusion imaging has been slowed by the lack or radiopharmaceuticals with suitable physical and biologic characteristics. Hexadecenoic acid, terminally labeled with 123I, partially overcomes these limitations by providing a compound that concentrates in the myocardium in proportion to relative regional blood flow and carries a gamma-emitter with desirable detection and imaging qualities. After intravenous injection in experimental animals, the clearance half-times of hexadecenoic acid for blood and myocardium are 1.7 and 20 min, respectively. These values compare favorably with 18-carbon fatty-acid analogs labeled with 11C. In acute and chronic infarction, similar distribution patterns are found for hexadecenoic acid and 43K, which indicates that hexadecenoic acid is a suitable substitute for the potassium analogs now in use for myocardial imaging. Because of the high count rates obtainable with 123I-hexadecenoic acid, good-guality images can be acquired in as little as 2-3 min per view. Iodine-123-hexadecenoic acid is potentially a useful radiopharmaceutical for clinical application.

  19. Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells

    PubMed Central

    Li, Yun; Fu, Jianxin; Ling, Yun; Yago, Tadayuki; McDaniel, J. Michael; Song, Jianhua; Bai, Xia; Kondo, Yuji; Qin, Yannan; Hoover, Christopher; McGee, Samuel; Shao, Bojing; Liu, Zhenghui; Sonon, Roberto; Azadi, Parastoo; Marth, Jamey D.; McEver, Rodger P.; Ruan, Changgeng; Xia, Lijun

    2017-01-01

    Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1−/−). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1−/− mice show reduced levels of α-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets. The preferential accumulation of HC C1galt1−/− platelets in the liver was reduced in mice lacking the hepatic asialoglycoprotein receptor [Ashwell–Morell receptor (AMR)]. However, we found that Kupffer cells are the primary cells phagocytosing HC C1galt1−/− platelets in the liver. Our results demonstrate that hepatic AMR promotes preferential adherence to and phagocytosis of desialylated and/or HC C1galt1−/− platelets by the Kupffer cell through its C-type lectin receptor CLEC4F. These findings provide insights into an essential role for core 1 O-glycosylation of platelets in their clearance in the liver. PMID:28716912

  20. Test of Cure for Anogenital Gonorrhoea Using Modern RNA-Based and DNA-Based Nucleic Acid Amplification Tests: A Prospective Cohort Study.

    PubMed

    Wind, Carolien M; Schim van der Loeff, Maarten F; Unemo, Magnus; Schuurman, Rob; van Dam, Alje P; de Vries, Henry J C

    2016-06-01

    The use of nucleic acid amplification tests (NAATs) to diagnose Neisseria gonorrhoeae infections complicates the performance of a test of cure (TOC) to monitor treatment failure, if this is indicated. As evidence for the timing of TOC using modern NAATs is limited, we performed a prospective cohort study to assess time to clearance when using modern RNA- and DNA-based NAATs. We included patients with anogenital gonorrhoea visiting the Sexually Transmitted Infection Clinic Amsterdam from March through October 2014. After treatment with ceftriaxone mono- or dual therapy (with azithromycin or doxycycline), anal, vaginal, or urine samples were self-collected during 28 consecutive days, and analyzed using an RNA-based NAAT (Aptima Combo 2) and a DNA-based NAAT (Cobas 4800). Clearance was defined as 3 consecutive negative results, and blips as isolated positive results following clearance. We included 77 patients; 5 self-cleared gonorrhoea before treatment and 10 were lost to follow-up. Clearance rate of the remaining 62 patients was 100%. Median time to clearance was 2 days, with a range of 1-7 days for RNA-based NAAT and 1-15 days for DNA-based NAAT. The risk of finding a blip after clearance was 0.8% and 1.5%, respectively. One patient had a reinfection. If indicated, we recommend that TOC be performed for anogenital gonorrhoea at least 7 or 14 days after administering therapy, when using modern RNA- or DNA-based NAATs, respectively. When interpreting TOC results for possible treatment failure, both the occurrence of blips and a possible reinfection need to be taken into account. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  1. Swing limb mechanics and minimum toe clearance in people with knee osteoarthritis.

    PubMed

    Levinger, Pazit; Lai, Daniel T H; Menz, Hylton B; Morrow, Adam D; Feller, Julian A; Bartlett, John R; Bergman, Neil R; Begg, Rezaul

    2012-02-01

    Knee osteoarthritis (OA) has been shown to be a risk factor for falls. Reductions in foot clearance during the swing phase of walking can cause a trip and potentially lead to a fall. This study examined the swing phase mechanics of people with and without knee OA during walking. Minimum toe clearance (MTC) height, joint angles at the time of MTC and the influence of the angular changes of the hip, knee and ankle of the swing leg on foot clearance using sensitivity analysis were investigated in 50 knee OA participants and 28 age-matched asymptomatic controls. Although both groups had a similar MTC height (controls: 12.8±6.7 mm, knee OA: 13.4±7.0 mm), the knee OA group used a different strategy to achieve the same foot clearance, as evidenced by greater knee flexion (52.5±5.3° vs 49.4±4.8°, p=0.007), greater hip abduction (-3.6±3.3° vs -1.8±3.3°, p=0.03) and less ankle adduction (2.8±1.9° vs 4.2±2.1°, p=0.01). MTC height was comparable between the groups, however a different swing phase mechanism was used by the knee OA. Although adequate MTC is an important component of safe locomotion, it does not appear to be impaired in people with knee OA. Other factors, such as inadequate responses to postural perturbation, may be responsible for falls in this group. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

  3. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 3 2013-04-01 2013-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

  4. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

  5. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

  6. 20 CFR 655.150 - Interstate clearance of job order.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 3 2014-04-01 2014-04-01 false Interstate clearance of job order. 655.150... job order. (a) SWA posts in interstate clearance system. The SWA must promptly place the job order in... transmit a copy of its active job order to all States listed in the job order as anticipated worksites...

  7. Dimerization of glycoprotein Ibα is not sufficient to induce platelet clearance.

    PubMed

    Liang, X; Syed, A K; Russell, S R; Ware, J; Li, R

    2016-02-01

    ESSENTIALS: Many anti-glycoprotein (GP)Ibα antibodies induce platelet clearance in a dimer-dependent manner. Characterization of monoclonal antibodies that bind the mechanosensitive domain (MSD) of GPIbα. An anti-MSD antibody binds two copies of GPIbα in platelets but does not induce platelet clearance. The prevailing clustering model of GPIbα signaling is incorrect or needs revision. The mechanism of platelet clearance is not clear. Many antibodies binding the membrane-distal ligand-binding domain of glycoprotein (GP)Ibα induce rapid clearance of platelets and acute thrombocytopenia, which requires the bifurcated antibody structure. It was thought that binding of these antibodies induced lateral dimerization or clustering of GPIbα in the plasma membrane, which leads to downstream signaling and platelet clearance. However, many antibodies targeting GPIbβ and GPIX, which are associated with GPIbα in the GPIb-IX complex, do not induce platelet clearance, which is in contradiction to the clustering model. To test whether dimerization or clustering of GPIbα is sufficient to transmit the signal that leads to platelet clearance. We have recently raised several mAbs targeting the mechanosensitive domain (MSD) of GPIbα. Binding of these anti-MSD antibodies was characterized with biochemical methods. Their ability to stimulate platelets and induce platelet clearance in mice was assessed. Infusion of anti-MSD antibodies does not cause thrombocytopenia in mice. These antibodies show no detectable effects on platelet activation and aggregation in vitro. Further biochemical investigation showed that the anti-MSD antibody 3D1 binds two copies of GPIbα on the platelet surface. Therefore, lateral dimerization of GPIbα induced by antibody binding is not sufficient to initiate GPIb-IX signaling and induce platelet clearance. Our results suggest that a factor other than or in addition to clustering of GPIbα is required to induce platelet clearance. © 2015 International

  8. HPT Clearance Control: Intelligent Engine Systems-Phase 1

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The following work has been completed to satisfy the Phase I Deliverables for the "HPT Clearance Control" project under NASA GRC's "Intelligent Engine Systems" program: (1) Need for the development of an advanced HPT ACC system has been very clearly laid out, (2) Several existing and potential clearance control systems have been reviewed, (3) A scorecard has been developed to document the system, performance (fuel burn, range, payload, etc.), thermal, and mechanical characteristics of the existing clearance control systems, (4) Engine size and flight cycle selection for the advanced HPT ACC system has been reviewed with "large engine"/"long range mission" combination showing the most benefit, (5) A scoring criteria has been developed to tie together performance parameters for an objective, data driven comparison of competing systems, and (6) The existing HPT ACC systems have been scored based on this scoring system.

  9. Genome-wide study of methotrexate clearance replicates SLCO1B1

    PubMed Central

    Ramsey, Laura B.; Panetta, John C.; Smith, Colton; Yang, Wenjian; Fan, Yiping; Winick, Naomi J.; Martin, Paul L.; Cheng, Cheng; Devidas, Meenakshi; Pui, Ching-Hon; Evans, William E.; Hunger, Stephen P.; Loh, Mignon

    2013-01-01

    Methotrexate clearance can influence the cure of and toxicity in children with acute lymphoblastic leukemia (ALL). We estimated methotrexate plasma clearance for 1279 patients with ALL treated with methotrexate (24-hour infusion of a 1 g/m2 dose or 4-hour infusion of a 2 g/m2 dose) on the Children's Oncology Group P9904 and P9905 protocols. Methotrexate clearance was lower in older children (P = 7 × 10−7), girls (P = 2.7 × 10−4), and those who received a delayed-intensification phase (P = .0022). A genome-wide analysis showed that methotrexate clearance was associated with polymorphisms in the organic anion transporter gene SLCO1B1 (P = 2.1 × 10−11). This replicates findings using different schedules of high-dose methotrexate in St Jude ALL treatment protocols; a combined meta-analysis yields a P value of 5.7 × 10−19 for the association of methotrexate clearance with SLCO1B1 SNP rs4149056. Validation of this variant with 5 different treatment regimens of methotrexate solidifies the robustness of this pharmacogenomic determinant of methotrexate clearance. This study is registered at http://www.clinicaltrials.gov as NCT00005585 and NCT00005596. PMID:23233662

  10. Inert gas clearance from tissue by co-currently and counter-currently arranged microvessels

    PubMed Central

    Lu, Y.; Michel, C. C.

    2012-01-01

    To elucidate the clearance of dissolved inert gas from tissues, we have developed numerical models of gas transport in a cylindrical block of tissue supplied by one or two capillaries. With two capillaries, attention is given to the effects of co-current and counter-current flow on tissue gas clearance. Clearance by counter-current flow is compared with clearance by a single capillary or by two co-currently arranged capillaries. Effects of the blood velocity, solubility, and diffusivity of the gas in the tissue are investigated using parameters with physiological values. It is found that under the conditions investigated, almost identical clearances are achieved by a single capillary as by a co-current pair when the total flow per tissue volume in each unit is the same (i.e., flow velocity in the single capillary is twice that in each co-current vessel). For both co-current and counter-current arrangements, approximate linear relations exist between the tissue gas clearance rate and tissue blood perfusion rate. However, the counter-current arrangement of capillaries results in less-efficient clearance of the inert gas from tissues. Furthermore, this difference in efficiency increases at higher blood flow rates. At a given blood flow, the simple conduction-capacitance model, which has been used to estimate tissue blood perfusion rate from inert gas clearance, underestimates gas clearance rates predicted by the numerical models for single vessel or for two vessels with co-current flow. This difference is accounted for in discussion, which also considers the choice of parameters and possible effects of microvascular architecture on the interpretation of tissue inert gas clearance. PMID:22604885

  11. Analysis of foot clearance in firefighters during ascent and descent of stairs.

    PubMed

    Kesler, Richard M; Horn, Gavin P; Rosengren, Karl S; Hsiao-Wecksler, Elizabeth T

    2016-01-01

    Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p < 0.05) post-exercise for nine of 12 ascent parameters and increased for two of eight descent parameters. Load carriage resulted in significantly decreased (p < 0.05) clearance over three ascent parameters, and one increase during descent. Decreased clearances during ascent caused by fatigue or load carriage may result in an increased trip risk. Increased clearances during descent may suggest use of a compensation strategy to ensure stair clearance or an increased risk of over-stepping during descent. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  12. 7 CFR 1927.53 - Costs of title clearance and closing of transactions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Costs of title clearance and closing of transactions... and Loan Closing § 1927.53 Costs of title clearance and closing of transactions. The borrower or the... payment of all costs of title clearance and closing of the transaction and will arrange for payment before...

  13. 76 FR 17182 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... Activities: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative... Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

  14. 76 FR 19359 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-07

    ... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

  15. Railway Tunnel Clearance Inspection Method Based on 3D Point Cloud from Mobile Laser Scanning

    PubMed Central

    Zhou, Yuhui; Wang, Shaohua; Mei, Xi; Yin, Wangling; Lin, Chunfeng; Mao, Qingzhou

    2017-01-01

    Railway tunnel clearance is directly related to the safe operation of trains and upgrading of freight capacity. As more and more railway are put into operation and the operation is continuously becoming faster, the railway tunnel clearance inspection should be more precise and efficient. In view of the problems existing in traditional tunnel clearance inspection methods, such as low density, slow speed and a lot of manual operations, this paper proposes a tunnel clearance inspection approach based on 3D point clouds obtained by a mobile laser scanning system (MLS). First, a dynamic coordinate system for railway tunnel clearance inspection has been proposed. A rail line extraction algorithm based on 3D linear fitting is implemented from the segmented point cloud to establish a dynamic clearance coordinate system. Second, a method to seamlessly connect all rail segments based on the railway clearance restrictions, and a seamless rail alignment is formed sequentially from the middle tunnel section to both ends. Finally, based on the rail alignment and the track clearance coordinate system, different types of clearance frames are introduced for intrusion operation with the tunnel section to realize the tunnel clearance inspection. By taking the Shuanghekou Tunnel of the Chengdu–Kunming Railway as an example, when the clearance inspection is carried out by the method mentioned herein, its precision can reach 0.03 m, and difference types of clearances can be effectively calculated. This method has a wide application prospects. PMID:28880232

  16. Clearance of the cervical spine in clinically unevaluable trauma patients.

    PubMed

    Halpern, Casey H; Milby, Andrew H; Guo, Wensheng; Schuster, James M; Gracias, Vicente H; Stein, Sherman C

    2010-08-15

    Meta-analytic costeffectiveness analysis. Our goal was to compare the results of different management strategies for trauma patients in whom the cervical spine was not clinically evaluable due to impaired consciousness, endotracheal intubation, or painful distracting injuries. We performed a structured literature review related to cervical spine trauma, radiographic clearance techniques (plain radiography, flexion/extension, CT, and MRI), and complications associated with semirigid collar use. Meta-analytic techniques were used to pool data from multiple sources to calculate pooled mean estimates of sensitivities and specificities of imaging techniques for cervical spinal clearance, rates of complications from various clearance strategies and from empirical use of semirigid collars. A decision analysis model was used to compare outcomes and costs among these strategies. Slightly more than 7.5% of patients who are clinically unevaluable have cervical spine injuries, and 42% of these injuries are associated with spinal instability. Sensitivity of plain radiography or fluoroscopy for spinal clearance was 57% (95% CI: 57%-60%). Sensitivities for CT and MRI alone were 83% (82%-84%) and 87% (84%-89%), respectively. Complications associated with collar use ranged from 1.3% (2 days) to 7.1% (10 days) but were usually minor and short-lived. Quadriplegia resulting from spinal instability missed by a clearance test had enormous impacts on longevity, quality of life, and costs. These impacts overshadowed the effects of prolonged collar application, even when the incidence of quadriplegia was extremely low. As currently used, neuroimaging studies for cervical spinal clearance in clinically unevaluable patients are not cost-effective compared with empirical immobilization in a semirigid collar.

  17. 75 FR 37738 - 1-Naphthaleneacetic Acid; Time-Limited Tolerance, Technical Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-30

    ...-Naphthaleneacetic Acid; Time-Limited Tolerance, Technical Correction AGENCY: Environmental Protection Agency (EPA..., ethylene oxide, fenvalerate, et al.; tolerance actions. Today's rule restores the time-limited tolerance...-3) establishing a time-limited tolerance for residues of 1-naphthaleneacetic acid ethyl ester in or...

  18. 76 FR 55078 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ...; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery...): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery'' to OMB for.... SUPPLEMENTARY INFORMATION: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service...

  19. 76 FR 39893 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ...; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery.... SUPPLEMENTARY INFORMATION: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service...

  20. [Study on compatibility of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma based on pharmacokinetics of effective components salvianolic acid B and ferulic acid in rat plasma].

    PubMed

    Zhang, Cui-ying; Zhang, Hong; Dong, Yu; Ren, Wei-guang; Chen, Heng-wen

    2015-04-01

    A study was made on the pharmacokinetic regularity of effective components salvianolic acid B and ferulic acid in Salviae Miltiorrhizae Radix et Rhizoma (SMRR) and Chuanxiong Rhizoma(CR) in rats, so as to discuss the compatibility mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Chuanxiong Rhizoma. Rats were randomly divided into three groups and intravenously injected with 50 mg x kg(-1) salvianolic acid B for the single SMRR extracts group, 0.5 mg x kg(-1) ferulic acid for the single CR extracts group and 50 mg x kg(-1) salvianolic acid B + 0.5 mg x kg(-1) ferulic acid for the SMRR and CR combination group. The blood samples were collected at different time points and purified by liquid-liquid extraction with ethyl acetate. With chloramphenicol as internal standard (IS), UPLC was adopted to determine concentrations of salvianolic acid B and ferulic acid. The pharmacokinetic parameters of salvianolic acid B and ferulic acid were calculated with WinNonlin 6.2 software and analyzed by SPSS 19.0 statistical software. The UPLC analysis method was adopted to determine salvianolic acid B and ferulic acid in rat plasma, including linear equation, stability, repeatability, precision and recovery. The established sample processing and analysis methods were stable and reliable, with significant differences in major pharmacokinetic parameters, e.g., area under the curve (AUC), mean residence time (MRT) and terminal half-life (t(1/2)). According to the experimental results, the combined application of SMRR and CR can significantly impact the pharmacokinetic process of their effective components in rats and promote the wide distribution, shorten the action time and prolong the in vivo action time of salvianolic acid B and increase the blood drug concentration and accelerate the clearance of ferulic acid in vivo.

  1. Effect of Internal Clearance on Load Distribution and Life of Radially Loaded Ball and Roller Bearings

    NASA Technical Reports Server (NTRS)

    Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

    2012-01-01

    The effect of internal clearance on radially loaded deepgroove ball and cylindrical roller bearing load distribution and fatigue life was determined for four clearance groups defined in the bearing standards. The analysis was extended to negative clearance (interference) conditions to produce a curve of life factor versus internal clearance. Rolling-element loads can be optimized and bearing life maximized for a small negative operating clearance. Life declines gradually with positive clearance and rapidly with increasing negative clearance. Relationships were found between bearing life and internal clearance as a function of ball or roller diameter, adjusted for load. Results are presented as life factors for radially loaded bearings independent of bearing size or applied load. In addition, a modified Stribeck Equation is presented that relates the maximum rolling-element load to internal bearing clearance.

  2. 76 FR 10626 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-25

    ... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY... Clearance for the Collection of Qualitative Feedback on Agency Service Delivery'' to OMB for approval under...: Title: Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery. Abstract...

  3. Cervical Spine Clearance in Pediatric Trauma Centers: The Need for Standardization and an Evidence-based Protocol.

    PubMed

    Pannu, Gurpal S; Shah, Mitesh P; Herman, Marty J

    combination of x-ray and computed tomographic imaging. Only 46% of institutions utilize a written, standardized pediatric cervical spine clearance protocol. This study demonstrates a striking variability in the use of personnel, imaging modalities and, most importantly, standardized protocol in the evaluation of the pediatric trauma patient with a potential cervical spine injury. Cervical spine clearance protocols have been shown to decrease the incidence of missed injuries, minimize excessive radiation exposure, decrease the time to collar removal, and lower overall associated costs. It is our opinion that development of a task force or multicenter research protocol that incorporates existing evidence-based literature is the next best step in improving the care of children with cervical spine injuries. Level 4-economic and decision analyses.

  4. Long-term clearance from small airways in subjects with ciliary dysfunction.

    PubMed

    Lindström, Maria; Falk, Rolf; Hjelte, Lena; Philipson, Klas; Svartengren, Magnus

    2006-05-20

    The objective of this study was to investigate if long-term clearance from small airways is dependent on normal ciliary function. Six young adults with primary ciliary dyskinesia (PCD) inhaled 111 Indium labelled Teflon particles of 4.2 microm geometric and 6.2 microm aerodynamic diameter with an extremely slow inhalation flow, 0.05 L/s. The inhalation method deposits particles mainly in the small conducting airways. Lung retention was measured immediately after inhalation and at four occasions up to 21 days after inhalation. Results were compared with data from ten healthy controls. For additional comparison three of the PCD subjects also inhaled the test particles with normal inhalation flow, 0.5 L/s, providing a more central deposition. The lung retention at 24 h in % of lung deposition (Ret24) was higher (p < 0.001) in the PCD subjects, 79 % (95% Confidence Interval, 67.6;90.6), compared to 49% (42.3;55.5) in the healthy controls. There was a significant clearance after 24 h both in the PCD subjects and in the healthy controls with equivalent clearance. The mean Ret24 with slow inhalation flow was 73.9 +/- 1.9% compared to 68.9 +/- 7.5% with normal inhalation flow in the three PCD subjects exposed twice. During day 7-21 the three PCD subjects exposed twice cleared 9% with normal flow, probably representing predominantly alveolar clearance, compared to 19% with slow inhalation flow, probably representing mainly small airway clearance. This study shows that despite ciliary dysfunction, clearance continues in the small airways beyond 24 h. There are apparently additional clearance mechanisms present in the small airways.

  5. Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

    PubMed

    Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

    2015-12-01

    Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. © 2015 Authors; published by Portland Press Limited.

  6. Application of a Pharmacokinetic Model of Metformin Clearance in a Population with Acute Myeloid Leukemia.

    PubMed

    Ceacareanu, Alice C; Brown, Geoffrey W; Moussa, Hoda A; Wintrob, Zachary A P

    2018-01-01

    We aimed to estimate the metformin-associated lactic acidosis (MALA) risk by assessing retrospectively the renal clearance variability and applying a pharmacokinetic (PK) model of metformin clearance in a population diagnosed with acute myeloid leukemia (AML) and diabetes mellitus (DM). All adults with preexisting DM and newly diagnosed AML at Roswell Park Cancer Institute were reviewed (January 2003-December 2010, n = 78). Creatinine clearance (CrCl) and total body weight distributions were used in a two-compartment PK model adapted for multiple dosing and modified to account for actual intra- and inter-individual variability. Based on this renal function variability evidence, 1000 PK profiles were simulated for multiple metformin regimens with the resultant PK profiles being assessed for safe CrCl thresholds. Metformin 500 mg up to three times daily was safe for all simulated profiles with CrCl ≥25 mL/min. Furthermore, the estimated overall MALA risk was below 10%, remaining under 5% for 500 mg given once daily. CrCl ≥65.25 mL/min was safe for administration in any of the tested regimens (500 mg or 850 mg up to three times daily or 1000 mg up to twice daily). PK simulation-guided prescribing can maximize metformin's beneficial effects on cancer outcomes while minimizing MALA risk.

  7. A novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of clearance of lipids in human tears.

    PubMed

    Napoli, Pietro Emanuele; Coronella, Franco; Satta, Giovanni Maria; Fossarello, Maurizio

    2014-01-01

    The aim of this work was to gather preliminary data in different conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD) individuals, using a new, contrast-enhanced optical coherence tomography (OCT) imaging method to evaluate the clearance of lipids in human tears. Eighty-two adult patients presenting with complaints of ocular irritation were studied for abnormalities of the ocular surface and classified as healthy (n = 21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion, was used to obtain an enhanced OCT imaging of the lower tear meniscus. After instillation, a dramatic initial increase of reflectivity of the lower tear meniscus was detected by OCT, followed by a decay back to baseline values over time. Based on this finding, the clearance of lipids was measured in real-time by Fourier-domain anterior segment OCT. The differences in the clearance of lipids among the four groups as well as the correlations between symptom questionnaire score, standardized visual scale test, fluorescein break-up time, ocular surface fluorescein staining score, Schirmer I test scores were found to be statistically significant. The individual areas under the curve of the clearance of lipids calculated by the receiver operating characteristic curve technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and specificity of lipid-enhanced OCT imaging. This new technique of contrast-enhanced OCT imaging of the tear film following lipid-based tracer instillation provides a measure of the clearance of lipids. The quantitative values found are in agreement with other methods of evaluation of the lacrimal system. An improvement of the clinician's ability in the diagnosis and understanding of abnormalities of the ocular surface may be achieved by this simple approach.

  8. The influences of tip clearance on the performance of nozzle blades of radial turbines - Experiment and performance prediction at three nozzle angles

    NASA Astrophysics Data System (ADS)

    Hyun, Yong-Ik; Yamaguchi, Michiteru; Hayami, Hiroshi; Senoo, Yasutoshi

    1988-05-01

    In order to study the influence of tip clearance on the turning angle and pressure loss of turbine nozzles, experimental results were obtained for nozzle angles at which the throat area was 0.8 and 1.4 times the rated condition. Contour maps of the total pressure loss and of the spanwise distributions of the mean exit-flow angle have been obtained. Although the two-layer flow model of Senoo et al., (1987) is shown to accurately predict the effects of tip clearance, it underestimates the clearance effect for a lightly loaded condition.

  9. Clearance of polonium-210-enriched cigarette smoke from the rat trachea and lung

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cohen, B.S.; Harley, N.H.; Tso, T.C.

    The distribution and clearance of alpha radioactivity in the lungs of rats were measured after inhalation of smoke from cigarettes highly enriched in /sup 210/Po. Female Fischer rats were exposed daily for 6 months to smoke from cigarettes with 500 times the normal content of /sup 210/Po. Control rats were exposed to standard cigarette smoke. Animals were serially withdrawn and killed. After necropsy the trachea, major bronchi, larynx, and nasopharynx were examined for surface alpha activity by an etched track technique utilizing cellulose nitrate detectors. Areas of accumulated activity were seen on samples of larynx from rats exposed to themore » /sup 210/Po-enriched cigarettes. No other local accumulations were seen on the airways. The lower lungs were analyzed radiochemically for /sup 210/Po. Both radiochemical analysis and track measurements showed highly elevated activity concentrations in rats exposed to the /sup 210/Po-enriched cigarettes. Following withdrawal from smoking, both short- and long-term clearance components were seen. The parameters which fit the postexposure data for clearance of the lung burden cannot fit the buildup during the exposure period.« less

  10. Seal Investigations of an Active Clearance Control System Concept

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.; Taylor, Shawn; Oswald, Jay; DeCastro, Jonathan A.

    2006-01-01

    In an effort to improve upon current thermal active clearance control methods, a first generation, fast-acting mechanically actuated, active clearance control system has been designed and installed into a non-rotating test rig. In order to harvest the benefit of tighter blade tip clearances, low-leakage seals are required for the actuated carrier segments of the seal shroud to prevent excessive leakage of compressor discharge (P3) cooling air. The test rig was designed and fabricated to facilitate the evaluation of these types of seals, identify seal leakage sources, and test other active clearance control system concepts. The objective of this paper is to present both experimental and analytical investigations into the nature of the face-seal to seal-carrier interface. Finite element analyses were used to examine face seal contact pressures and edge-loading under multiple loading conditions, varied E-seal positions and two new face seal heights. The analyses indicated that moving the E-seal inward radially and reducing face seal height would lead to more uniform contact conditions between the face seal and the carriers. Lab testing confirmed that moving the balance diameter inward radially caused a decrease in overall system leakage.

  11. Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study.

    PubMed

    Kurth, Florian; Develoux, Michel; Mechain, Matthieu; Clerinx, Jan; Antinori, Spinello; Gjørup, Ida E; Gascon, Joaquím; Mørch, Kristine; Nicastri, Emanuele; Ramharter, Michael; Bartoloni, Alessandro; Visser, Leo; Rolling, Thierry; Zanger, Philipp; Calleri, Guido; Salas-Coronas, Joaquín; Nielsen, Henrik; Just-Nübling, Gudrun; Neumayr, Andreas; Hachfeld, Anna; Schmid, Matthias L; Antonini, Pietro; Pongratz, Peter; Kern, Peter; Saraiva da Cunha, José; Soriano-Arandes, Antoni; Schunk, Mirjam; Suttorp, Norbert; Hatz, Christoph; Zoller, Thomas

    2015-11-01

    Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Effect of the presence of dental plaque on oral sugar clearance and salivary pH: an in vivo study.

    PubMed

    Pradhan, Debapriya; Jain, Deepak; Gulati, Amit; Kolhe, Swapnil J; Baad, Rajendra; Rao, B Sunil

    2012-11-01

    Fermentable carbohydrates and microorganisms in the plaque play a significant role in the pathogenesis of dental caries. Oral clearance of sugars and salivary pH is affected by the presence of plaque. This study was conducted to study the effect of the presence of plaque on the salivary clearance of sucrose and on salivary pH. The study design was of a randomized controlled parallel group clinical trial and included two groups: The control group and plaque group, as follows: Control group--subjects without plaque and plaque group--subjects with plaque. Salivary sucrose determination was done by using the anthrone technique. A digital pH meter estimated the salivary pH. The Student's t test and Mann-Whitney test was employed to compare the intergroup differences. Pearson's correlation coefficient was used for analysis. The salivary sucrose clearance time was increased by presence of plaque. The presence of plaque led to increased salivary sucrose concentrations and increased the salivary sucrose clearance time. The dental caries is the dynamic relationship among the dental plaque microbiota, dietary carbohydrates, saliva and cariogenic potential of the dental plaque. Caries occur preferentially in the dentition sites characterized by high exposure to carbohydrate and diminished salivary effect.

  13. 14 CFR 25.925 - Propeller clearance.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... attitude, whichever is most critical. In addition, there must be positive clearance between the propeller and the ground when in the level takeoff attitude with the critical tire(s) completely deflated and...

  14. 30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

  15. 30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

  16. 30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

  17. 30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

  18. 30 CFR 56.11005 - Fixed ladder anchorage and toe clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Fixed ladder anchorage and toe clearance. 56.11005 Section 56.11005 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Travelways § 56.11005 Fixed ladder anchorage and toe clearance. Fixed ladders shall be anchored securely and...

  19. Impairment of paravascular clearance pathways in the aging brain.

    PubMed

    Kress, Benjamin T; Iliff, Jeffrey J; Xia, Maosheng; Wang, Minghuan; Wei, Helen S; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason A; Plog, Benjamin A; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

    2014-12-01

    In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. © 2014 American Neurological Association.

  20. Zone clearance in an infinite TASEP with a step initial condition

    NASA Astrophysics Data System (ADS)

    Cividini, Julien; Appert-Rolland, Cécile

    2017-06-01

    The TASEP is a paradigmatic model of out-of-equilibrium statistical physics, for which many quantities have been computed, either exactly or by approximate methods. In this work we study two new kinds of observables that have some relevance in biological or traffic models. They represent the probability for a given clearance zone of the lattice to be empty (for the first time) at a given time, starting from a step density profile. Exact expressions are obtained for single-time quantities, while more involved history-dependent observables are studied by Monte Carlo simulation, and partially predicted by a phenomenological approach.

  1. Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients.

    PubMed

    Alves, Camila Fernanda da Silveira; Grott, Camila Schultz; Lunge, Vagner Ricardo; Béria, Jorge Umberto; Tietzmann, Daniela Cardoso; Stein, Airton Tetelbom; Simon, Daniel

    2016-01-01

    Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients.

  2. Interferon lambda 4 (IFNL4) gene polymorphism is associated with spontaneous clearance of HCV in HIV-1 positive patients

    PubMed Central

    Alves, Camila Fernanda da Silveira; Grott, Camila Schultz; Lunge, Vagner Ricardo; Béria, Jorge Umberto; Tietzmann, Daniela Cardoso; Stein, Airton Tetelbom; Simon, Daniel

    2016-01-01

    Abstract Approximately one-third of the individuals infected with human immunodeficiency virus type 1 (HIV-1) are co-infected with hepatitis C virus (HCV). Co-infected patients have an increased risk for developing end-stage liver diseases. Variants upstream of the IFNL3 gene have been associated with spontaneous and treatment-induced clearance of HCV infection. Recently, a novel polymorphism was discovered, denoted IFNL4 ΔG > TT (rs368234815), which seems to be a better predictor of spontaneous clearance than the IFNL4 rs12979860 polymorphism. We aimed to determine the prevalence of the IFNL4 ΔG > TT variants and to evaluate the association with spontaneous clearance of HCV infection in Brazilian HIV-1 patients. The IFNL4 ΔG > TT genotypes were analyzed by polymerase chain reaction followed by restriction digestion in 138 HIV-1 positive patients who had an anti-HCV positive result. Spontaneous clearance of HCV was observed in 34 individuals (24.6%). IFNL4 genotype distribution was significantly different between individuals who had spontaneous clearance and chronic HCV patients (p=0.002). The probability of spontaneous clearance of HCV infection for patients with the IFNL4 TT/TT genotype was 3.6 times higher than for patients carrying the IFNL4 ΔG allele (OR=3.63, 95% CI:1.51-8.89, p=0.001). The IFNL4 ΔG > TT polymorphism seems to be better than IFNL4 rs12979860 to predict spontaneous clearance of the HCV in Brazilian HIV-1 positive patients. PMID:27560987

  3. Poly(Lactic Acid) Hemodialysis Membranes with Poly(Lactic Acid)-block-Poly(2-Hydroxyethyl Methacrylate) Copolymer As Additive: Preparation, Characterization, and Performance.

    PubMed

    Zhu, Lijing; Liu, Fu; Yu, Xuemin; Xue, Lixin

    2015-08-19

    Poly(lactic acid) (PLA) hemodialysis membranes with enhanced antifouling capability and hemocompatibility were developed using poly(lactic acid)-block-poly(2-hydroxyethyl methacrylate) (PLA-PHEMA) copolymers as the blending additive. PLA-PHEMA block copolymers were synthesized via reversible addition-fragmentation (RAFT) polymerization from aminolyzed PLA. Gel permeation chromatography (GPC) and (1)H-nuclear magnetic resonance ((1)H NMR) were applied to characterize the synthesized products. By blending PLA with the amphiphilic block copolymer, PLA/PLA-PHEMA membranes were prepared by nonsolvent induced phase separation (NIPS) method. Their chemistry and structure were characterized with X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM) and atomic force microscopy (AFM). The results revealed that PLA/PLA-PHEMA membranes with high PLA-PHEMA contents exhibited enhanced hydrophilicity, water permeability, antifouling and hemocompatibility. Especially, when the PLA-PHEMA concentration was 15 wt %, the water flux of the modified membrane was about 236 L m(-2) h(-1). Its urea and creatinine clearance was more than 0.70 mL/min, lysozyme clearance was about 0.50 mL/min, BSA clearance was as less as 0.31 mL/min. All the results suggest that PLA-PHEMA copolymers had served as effective agents for optimizing the property of PLA-based membrane for hemodialysis applications.

  4. Comparison between intraoperative cholangiography and choledochoscopy for ductal clearance in laparoscopic CBD exploration: a prospective randomized study.

    PubMed

    Vindal, Anubhav; Chander, Jagdish; Lal, Pawanindra; Mahendra, Balu

    2015-05-01

    Laparoscopic CBD exploration (LCBDE) is an accepted treatment modality for single stage management of CBD stones in fit patients. A transcholedochal approach is preferred in patients with a dilated CBD and large impacted stones in whom ductal clearance remains problematic. There are very few studies comparing intraoperative cholangiography (IOC) with choledochoscopy to determine ductal clearance in patients undergoing transcholedochal LCBDE. This series represents the first of those comparing the two from Asia. Between April 2009 and October 2012, 150 consecutive patients with CBD stones were enrolled in a prospective randomized study to undergo transcholedochal LCBDE on an intent-to-treat basis. Patients with CBD diameter of less than 9 mm on preoperative imaging were excluded from the study. Out of the 132 eligible patients, 65 patients underwent IOC (Group A), and 67 patients underwent intraoperative choledochoscopy (Group B) to determine CBD clearance. There were no differences between the two groups in the demographic profile and the preoperative biochemical findings. There was no conversion to open procedures, and complete stone clearance was achieved in all the 132 cases. The mean CBD diameter and the mean number of CBD stones removed were comparable between the two groups. Mean operating time was 170 min in Group A and 140 min in Group B (p < 0.001). There was no difference in complications between the two groups. Nine patients in Group A (13.8%) showed non-passage of contrast into the duodenum on IOC which resolved after administration of i.v. glucagon, suggesting a transient spasm of sphincter of Oddi. Two patients (3%) showed a false-positive result on IOC which had to be resolved with choledochoscopy. The present study showed that intraoperative choledochoscopy is better than IOC for determining ductal clearance after transcholedochal LCBDE and is less cumbersome and less time-consuming.

  5. Hepatic macrophage complement receptor clearance function following injury.

    PubMed

    Cuddy, B G; Loegering, D J; Blumenstock, F A; Shah, D M

    1986-03-01

    Previous work has demonstrated that in vivo hepatic macrophage complement receptor clearance function is depressed following thermal injury. The present study was carried out to determine if complement receptor function depression is associated with other states of depressed host defense. Hepatic complement receptor clearance function was determined from the hepatic uptake of rat erythrocytes coated with antierythrocyte IgM (EIgM) in rats. Receptor function was determined following cannulation of a carotid artery, laparotomy plus enterotomy, hemorrhagic shock, trauma, thermal injury, acute bacteremia, acute endotoxemia, and injection of erythrocyte stroma, gelatinized lipid emulsion, or colloidal carbon. Hepatic uptake of EIgM was depressed following each of these experimental interventions except arterial cannulation. This effect was shown not to be due to a decrease in hepatic blood flow or depletion of complement and was therefore due to a depression in hepatic macrophage complement receptor clearance function. Thus, impairment of hepatic macrophage complement receptor function is associated with several states of depressed host defense.

  6. Experimental Study of Unshrouded Impeller Pump Stage Sensitivity to Tip Clearance

    NASA Technical Reports Server (NTRS)

    Williams, Robert W.; Zoladz, Thomas; Storey, Anne K.; Skelley, Stephen E.

    2002-01-01

    This viewgraph presentation provides information on an experiment. Its objective is to experimentally determine unshrouded impeller performance sensitivity to tip clearance. The experiment included: Determining impeller efficiency at scaled operating conditions in water at MSFC's Pump Test Equipment (PTE) Facility; Testing unshrouded impeller at three different tip clearances; Testing each tip clearance configuration at on- and off-design conditions, and collecting unsteady- and steady-state data in each configuration; Determining impeller efficiency directly using drive line torquemeter and pump inlet and exit total pressure measurements.

  7. 14 CFR 103.23 - Flight visibility and cloud clearance requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

  8. 14 CFR 103.23 - Flight visibility and cloud clearance requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

  9. 14 CFR 103.23 - Flight visibility and cloud clearance requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

  10. 14 CFR 103.23 - Flight visibility and cloud clearance requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

  11. 14 CFR 103.23 - Flight visibility and cloud clearance requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Flight visibility and cloud clearance... Flight visibility and cloud clearance requirements. No person may operate an ultralight vehicle when the flight visibility or distance from clouds is less than that in the table found below. All operations in...

  12. Kinematics Simulation Analysis of Packaging Robot with Joint Clearance

    NASA Astrophysics Data System (ADS)

    Zhang, Y. W.; Meng, W. J.; Wang, L. Q.; Cui, G. H.

    2018-03-01

    Considering the influence of joint clearance on the motion error, repeated positioning accuracy and overall position of the machine, this paper presents simulation analysis of a packaging robot — 2 degrees of freedom(DOF) planar parallel robot based on the characteristics of high precision and fast speed of packaging equipment. The motion constraint equation of the mechanism is established, and the analysis and simulation of the motion error are carried out in the case of turning the revolute clearance. The simulation results show that the size of the joint clearance will affect the movement accuracy and packaging efficiency of the packaging robot. The analysis provides a reference point of view for the packaging equipment design and selection criteria and has a great significance on the packaging industry automation.

  13. Plasma Creatinine Clearance in the Dog

    ERIC Educational Resources Information Center

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  14. Active clearance control system for a turbomachine

    NASA Technical Reports Server (NTRS)

    Johnston, R. P.; Knapp, M. H.; Coulson, C. E. (Inventor)

    1982-01-01

    An axial compressor is provided with a cooling air manifold surrounding a portion of the shroud, and means for bleeding air from the compressor to the manifold for selectively flowing it in a modulating manner axially along the outer side of the stator/shroud to cool and shrink it during steady state operating conditions so as to obtain minimum shroud/rotor clearance conditions. Provision is also made to selectively divert the flow of cooling air from the manifold during transient periods of operation so as to alter the thermal growth or shrink rate of the stator/shroud and result in adequate clearance with the compressor rotor.

  15. Ocular silicon distribution and clearance following intravitreal injection of porous silicon microparticles

    PubMed Central

    Nieto, Alejandra; Hou, Huiyuan; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2013-01-01

    Porous silicon (pSi) microparticles have been investigated for intravitreal drug delivery and demonstrated good biocompatibility. With the appropriate surface chemistry, pSi can reside in vitreous for months or longer. However, ocular distribution and clearance pathway of its degradation product, silicic acid, are not well understood. In the current study, rabbit ocular tissue was collected at different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe simultaneous microdialysis of aqueous and vitreous humor was performed following a bolus intravitreal injection of 0.25 mL silicic acid (150 μg/mL) and six consecutive microdialysates were collected every 20 min. Silicon was quantified from the samples using inductively coupled plasma-optical emission spectroscopy. The study showed that following the intravitreal injection of oxidized pSi, free silicon was consistently higher in the aqueous than in the retina (8.1 ± 6.5 vs. 3.4 ± 3.9 μg/mL, p = 0.0031). The area under the concentration-time curve (AUC) of the retina was only about 24% that of the aqueous. The mean residence time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18 days for plasma. Similarly, following intravitreal fresh pSi, free silicon was also found higher in aqueous than in retina (7 ± 4.7 vs. 3.4 ± 4.1 μg/mL, p = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The microdialysis revealed the terminal half-life of free silicon in the aqueous was 30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the AUC for vitreous. Our studies indicate that aqueous humor is a significant pathway for silicon egress from the eye following intravitreal injection of pSi crystals. PMID:24036388

  16. Dexmedetomidine metabolic clearance is not affected by fat mass in obese patients.

    PubMed

    Rolle, A; Paredes, S; Cortínez, L I; Anderson, B J; Quezada, N; Solari, S; Allende, F; Torres, J; Cabrera, D; Contreras, V; Carmona, J; Ramírez, C; Oliveros, A M; Ibacache, M

    2018-05-01

    Obesity has been associated with reduced dexmedetomidine clearance, suggesting impaired hepatic function or reduced hepatic blood flow. The aim of this study was to clarify the effect of obesity in dexmedetomidine metabolic clearance. Forty patients, ASA I-III, 18-60 yr old, weighing 47-126 kg, scheduled for abdominal laparoscopic surgery, were enrolled. Anaesthetic agents (propofol, remifentanil, and dexmedetomidine) were dosed based on lean body weight measured by dual X-ray absorptiometry. Serial venous samples were drawn during and after dexmedetomidine infusion. A pharmacokinetic analysis was undertaken using non-linear mixed-effect models. In the modelling approach, the total body weight, lean body weight, and adjusted body weight were first tested as size descriptors for volumes and clearances. Hepatic blood flow, liver histopathology, liver enzymes, and gene expression of metabolic enzymes (UGT2B10 and UGT1A4) were tested as covariates of dexmedetomidine metabolic clearance. A decrease in NONMEM objective function value (ΔOFV) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. A total of 637 dexmedetomidine serum samples were obtained. A two-compartmental model scaled to measured lean weight adequately described the dexmedetomidine pharmacokinetics. Liver blood flow was a covariate for dexmedetomidine clearance (ΔOFV=-5.878). Other factors, including fat mass, histopathological damage, and differential expression of enzymes, did not affect the dexmedetomidine clearance in the population studied (ΔOFV<3.84). We did not find a negative influence of obesity in dexmedetomidine clearance when doses were adjusted to lean body weight. Liver blood flow showed a significant effect on dexmedetomidine clearance. NCT02557867. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

  17. Supine lung clearance of Tc-99m DTPA and HMPAO aerosols

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chia-Hung Kao; Hui-Tzu Lin; Shu-Ling Yu

    1995-07-01

    The speed of Tc-99m DTPA/HMPAO radioaerosol clearance from the lungs that is represented as a slope from lungs to blood was measured in 23 male normal controls using commercial lung radioaerosol delivery units in the supine position in order to avoid the influences of gravity. The right lung was selected and three regions of interest were created for equal subdivisions of the upper, middle, and lower third. The results show that the clearance of Tc-99m DTPA/HMPAO aerosols in the upper lung is lowest. The difference between upper and lower lungs for Tc-99m DTPA/HMPAO aerosol clearances are significant. The clearance ofmore » Tc-99m DTPA aerosols was significantly faster than those of Tc-99m HMPAO in any region. The authors conclude that, although the effect of gravity disappears in the supine position in our study, the differences of aerosol clearance in different regions are still significant. Lipophilic Tc-99m HMPAO aerosols were slower than those of hydrophilic Tc-99m DTPA, which suggests there are at least two different mechanisms. 22 refs., 2 figs., 1 tab.« less

  18. Impairment of nasal mucociliary clearance in woodworkers in the furniture industry

    PubMed Central

    Black, A.; Evans, J. C.; Hadfield, Esme H.; Macbeth, R. G.; Morgan, A.; Walsh, M.

    1974-01-01

    Black, A., Evans, J. C., Hadfield, Esme H., Macbeth, R. G., Morgan, A., and Walsh, M. (1974).British Journal of Industrial Medicine,31, 10-17. Impairment of nasal mucociliary clearance in woodworkers in the furniture industry. Measurements of mucociliary clearance from the anterior end of the middle turbinate were made using technetium-99m-labelled particles in nine woodworkers from the furniture industry and in 12 controls, none of whom had been occupationally exposed to wood dust. Clearance rates in the controls ranged from 1·9 to 18·5 mm min-1 with a mean of 6·8. These values are in good agreement with measurements reported elsewhere for normal subjects. Only one of the woodworkers had a clearance rate which fell within the normal range and he had been occupationally exposed for the shortest period (6 years). In four woodworkers clearance was very slow (< 1 mm min-1) and in three there was almost complete stasis. The results of this preliminary investigation suggest that nasal mucociliary function is significantly impaired in workers who have been exposed to wood dust in the furniture industry for more than 10 years. PMID:4821406

  19. Lung clearance index is a repeatable and sensitive indicator of radiological changes in bronchiectasis.

    PubMed

    Rowan, Stephen A; Bradley, Judy M; Bradbury, Ian; Lawson, John; Lynch, Tom; Gustafsson, Per; Horsley, Alex; O'Neill, Katherine; Ennis, Madeleine; Elborn, J Stuart

    2014-03-01

    In bronchiectasis there is a need for improved markers of lung function to determine disease severity and response to therapy. To assess whether the lung clearance index is a repeatable and more sensitive indicator of computed tomography (CT) scan abnormalities than spirometry in bronchiectasis. Thirty patients with stable bronchiectasis were recruited and lung clearance index, spirometry, and health-related quality of life measures were assessed on two occasions, 2 weeks apart when stable (study 1). A separate group of 60 patients with stable bronchiectasis was studied on a single visit with the same measurements and a CT scan (study 2). In study 1, the intervisit intraclass correlation coefficient for the lung clearance index was 0.94 (95% confidence interval, 0.89 to 0.97; P < 0.001). In study 2, the mean age was 62 (10) years, FEV1 76.5% predicted (18.9), lung clearance index 9.1 (2.0), and total CT score 14.1 (10.2)%. The lung clearance index was abnormal in 53 of 60 patients (88%) and FEV1 was abnormal in 37 of 60 patients (62%). FEV1 negatively correlated with the lung clearance index (r = -0.51, P < 0.0001). Across CT scores, there was a relationship with the lung clearance index, with little evidence of an effect of FEV1. There were no significant associations between the lung clearance index or FEV1 and health-related quality of life. The lung clearance index is repeatable and a more sensitive measure than FEV1 in the detection of abnormalities demonstrated on CT scan. The lung clearance index has the potential to be a useful clinical and research tool in patients with bronchiectasis.

  20. Novel sensors to enable closed-loop active clearance control in gas turbine engines

    NASA Astrophysics Data System (ADS)

    Geisheimer, Jonathan; Holst, Tom

    2014-06-01

    Active clearance control within the turbine section of gas turbine engines presents and opportunity within aerospace and industrial applications to improve operating efficiencies and the life of downstream components. Open loop clearance control is currently employed during the development of all new large core aerospace engines; however, the ability to measure the gap between the blades and the case and close down the clearance further presents as opportunity to gain even greater efficiencies. The turbine area is one of the harshest environments for long term placement of a sensor in addition to the extreme accuracy requirements required to enable closed loop clearance control. This paper gives an overview of the challenges of clearance measurements within the turbine as well as discusses the latest developments of a microwave sensor designed for this application.

  1. Does sleep disturbance affect the amyloid clearance mechanisms in Alzheimer's disease?

    PubMed

    Yulug, Burak; Hanoglu, Lutfu; Kilic, Ertugrul

    2017-10-01

    Sleep is an important factor that plays a key role in Alzheimer's disease pathogenesis. However, it is still unclear whether poor-quality sleep may overlap with sleep disturbances in the underlying dysfunctional mechanisms of amyloid beta (Aβ) clearance metabolism. Here, we aimed to evaluate the current evidence on the role of sleep deprivation in Aβ clearance metabolism. To that end, we discuss possible mechanisms underlying the bidirectional interaction between the sleep deprivation and Aβ clearance pathways. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  2. 76 FR 59379 - Proposed Information Collection; Comment Request; Generic Clearance for Research in Development...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ...-XXXX. Type of Review: Generic Clearance Request. Title: Generic Clearance for Research in Development..., filing of petitions and applications and agency #0;statements of organization and functions are examples... Proposed Information Collection; Comment Request; Generic Clearance for Research in Development of...

  3. Iodophenylpentadecanoic acid-myocardial blood flow relationship during maximal exercise with coronary occlusion.

    PubMed

    Caldwell, J H; Martin, G V; Link, J M; Krohn, K A; Bassingthwaighte, J B

    1990-01-01

    Imaging 123I-labeled iodophenylpentadecanoic acid (IPPA) uptake and clearance from the myocardium following exercise has been advocated as a means of detecting myocardial ischemia because fatty acid deposition is enhanced and clearance prolonged in regions of low flow. However, normal regional myocardial blood flows are markedly heterogeneous, and it is not known how this heterogeneity affects regional metabolism or substrate uptake and thus image interpretation. In five instrumented dogs running at near maximal workload on a treadmill, 131I-labeled IPPA and 15-micron 46Sc microspheres were injected into the left atrium after 30 sec of circumflex coronary artery occlusion. Microsphere and IPPA activity were determined in 250 mapped pieces of myocardium of approximately 400 mg. Myocardial blood flows (from microspheres) ranged from 0.05 to 7.6 ml/min/g. Deposition of IPPA was proportional to regional flows (r = 0.83) with an average retention of 25%. The mean endocardial-epicardial ratio for IPPA (0.90 +/- 0.43) was similar to that for microspheres (0.94 +/- 0.47; p = 0.08). Thus, initial IPPA deposition during treadmill exercise increases in proportion to regional myocardial blood flow over a range of flows from very low to five times normal.

  4. Impairment of paravascular clearance pathways in the aging brain

    PubMed Central

    Kress, Benjamin T.; Iliff, Jeffrey J.; Xia, Maosheng; Wang, Minghuan; Wei, Helen; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason; Plog, Benjamin A.; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

    2014-01-01

    Objective In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal and interstitial fluids. Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular cerebrospinal fluid (CSF) pathways. The Objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy while interstitial solute clearance was evaluated by radio-tracer clearance assays in young (2–3 month), middle age (10–12 month) and old (18–20 month) wild type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function were evaluated by immunofluorescence. Results Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparechamally injected amyloid β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. Interpretation We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of mis-folded protein aggregates. PMID:25204284

  5. Effect of Timing of Proton Pump Inhibitor Administration on Acid Suppression.

    PubMed

    Furuta, Kenji; Adachi, Kyoichi; Aimi, Masahito; Shimura, Shino; Mikami, Hironobu; Nishimura, Nobuhiro; Ishimura, Norihisa; Ishihara, Shunji; Naora, Kohji; Kinoshita, Yoshikazu

    2016-01-01

    Esomeprazole has been reported to show a strong acid suppression following preprandial as compared to postprandial administration, though no known study has compared the acid suppressing effects of other proton pump inhibitors between those administrations. The aim of this study was to compare intragastric pH levels following pre- and postprandial administrations of rabeprazole and esomeprazole. In 15 Helicobacter pylori-negative healthy volunteers, we measured intragastric pH after 7 days of pre- and postprandial administrations of rabeprazole (10 mg) or esomeprazole (20 mg) using a 5-way crossover design. Preprandial administration of esomeprazole showed stronger acid suppression than postprandial administration. The values for percent time at pH >4.0 over a 24-hour period increased from 45.3% with postprandial administration of esomeprazole to 54.4% with preprandial administration, while the percent time at pH >4.0 during daytime was increased to a greater extent from 51.4 to 66.5% with preprandial administration (p = 0.05). On the other hand, the acid suppressing effect of rabeprazole was not influenced by the timing of administration. The acid suppressing effect of esomeprazole is influenced by administration timing. In contrast, the acid suppressing effect of rabeprazole is not augmented by preprandial administration. © 2015 S. Karger AG, Basel.

  6. Experimental study on the sealing clearance between the labyrinth sealing displacer and cylinder in the 10 K G-M refrigerator

    NASA Astrophysics Data System (ADS)

    Hao, X. H.; Ju, Y. L.; Lu, Y. J.

    2011-05-01

    The labyrinth sealing displacer has been optimal designed to improve the operating stability and life-time of 10 K G-M refrigerator. The displacer was made of stainless steel 304 or inconel 718, coated with PTFE on its outer surface. Compared to the traditional piston-ring sealing displacer, the sealing clearance between the ridge of the labyrinth sealing displacer and cylinder is critical to the cooling performance of the G-M refrigerator. The displacers with different sealing clearances were experimentally studied, and the optimal clearance was given. The effects of the materials of the displacers and the system charge pressures on the performance of the labyrinth sealing were also tested and analyzed.

  7. Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar® in Children with Acute Lymphoblastic Leukemia.

    PubMed

    Würthwein, Gudrun; Lanvers-Kaminsky, Claudia; Hempel, Georg; Gastine, Silke; Möricke, Anja; Schrappe, Martin; Karlsson, Mats O; Boos, Joachim

    2017-12-01

    The pharmacokinetics of the polyethylene glycol (PEG)-conjugated asparaginase Oncaspar ® are characterized by an increase in elimination over time. The focus of our analysis is the better understanding of this time-dependency. In paediatric acute lymphoblastic leukemia therapy (AIEOP-BFM ALL 2009), two administrations of Oncaspar ® (2500 U/m 2 intravenously) in induction phase (14-day interval) and one single administration in reinduction were followed by weekly monitoring of asparaginase activity. Non-linear mixed-effects modeling techniques (NONMEM) were used. Samples indicating immunological inactivation were excluded to describe the pharmacokinetics under standard conditions. Models with time-constant or time-varying clearance (CL) as well as transit compartment models with an increase in CL over a chain of compartments were investigated. Models with time-constant elimination could not adequately describe 6107 asparaginase activities from 1342 patients. Implementing a time-varying CL improved the fit. Modeling an increase of CL over time after dose (E max - and Weibull-functions) were superior to models with an increase of CL over time after the first administration. However, a transit compartment model came out to be the best structural model. The increase in elimination of PEGylated asparaginase appears to be driven by physicochemical processes that are drug-related. The observed hydrolytically in vitro instability of the drug leads to the hypothesis that this increase in CL might be due to an in vivo hydrolysis of the instable ester bond between PEG and the enzyme combined with an increased elimination of the partly de-PEGylated enzyme (Trial registered at www.clinicaltrials.gov , NCT0111744).

  8. Incidence, clearance, and disease progression of genital human papillomavirus infection in heterosexual men.

    PubMed

    Moreira, Edson Duarte; Giuliano, Anna R; Palefsky, Joel; Flores, Carlos Aranda; Goldstone, Stephen; Ferris, Daron; Hillman, Richard J; Moi, Harald; Stoler, Mark H; Marshall, Brooke; Vuocolo, Scott; Guris, Dalya; Haupt, Richard M

    2014-07-15

    In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Effects of block copolymer properties on nanocarrier protection from in vivo clearance

    PubMed Central

    D’Addio, Suzanne M.; Saad, Walid; Ansell, Steven M.; Squiers, John J.; Adamson, Douglas; Herrera-Alonso, Margarita; Wohl, Adam R.; Hoye, Thomas R.; Macosko, Christopher W.; Mayer, Lawrence D.; Vauthier, Christine; Prud’homme, Robert K.

    2012-01-01

    Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to pathological tissues. There is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we produce nanocarriers with dense PEG layers resulting from block copolymer-directed assembly during rapid precipitation. Nanocarriers are formed using block copolymers with hydrophobic blocks of polystyrene (PS), poly-ε-caprolactone (PCL), poly-D,L-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with molecular weights from 1.5 kg/mol to 9 kg/mol. Nanocarriers with paclitaxel prodrugs are evaluated in vivo in Foxn1nu mice to determine relative rates of clearance. The amount of nanocarrier in circulation after 4 h varies from 10% to 85% of initial dose, depending on the block copolymer. In vitro complement activation assays are conducted in an effort to correlate the protection of the nanocarrier surface from complement binding and activation and in vivo circulation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly are proposed, relating to the relative size of the hydrophilic and hydrophobic block, the hydrophobicity of the anchoring block, the absolute size of the PEG block, and polymer crystallinity. The in vitro results distinguish between the poorly circulating PEG5k-PCL9k and the better circulating nanocarriers, but could not rank the better circulating nanocarriers in order of circulation time. Analysis of PEG surface packing on monodisperse 200 nm latex spheres indicates that the sizes of the hydrophobic PCL, PS, and PLA blocks are correlated with the PEG blob size, and possibly the clearance from circulation. Suggestions for next step in vitro measurements are made. PMID:22732478

  10. Impact of food on hepatic clearance of patients after endoscopic sphincterotomy.

    PubMed

    Chan, Hoi-Hung; Lai, Kwok-Hung; Lin, Chiun-Ku; Tsai, Wei-Lun; Peng, Nan-Jing; Hsu, Ping-I; Lo, Gin-Ho; Wei, Min-Ching; Wang, E-Ming; Chang, Hsueh-Wen

    2009-01-01

    The recurrence rate of common bile duct stones (CBDS) is around 3-21% after treatment by endoscopic sphincterotomy (ES). Fatty meal has been shown to improve hepatic clearance in both patients with intact gallbladder and post-cholecystectomy after ES. This study tested the effects of different kinds of food on hepatic clearance by using quantitative cholescintigraphy (QC) in patients after ES. Forty-seven patients after ES with abnormal QC were enrolled in our study. Complete ablation of sphincter function was confirmed by sphincter of Oddi manometry. Fasting QC was done in every patient shortly after normalization of liver function, and then followed with low-fat and fatty-meal QC. Each of the 47 subjects was observed for the effect on hepatic clearance at 3 different levels of treatments (diets and fasting). Additionally, possible factors responsible for recurrent CBDS were investigated by means of logistic regression. Both fatty and low-fat meals could significantly improve hepatic clearance compared with fasting in most patients after ES. But the response to food types was individualized. All patients tolerated the meals well. There was no significant relationship between the recurrence of CBDS and sex, age, intact gallbladder and presence of juxtapapillary diverticulum, CBD size, and improvement in hepatic clearance (> or = 5%) by food. Both fatty and low-fat meals improved hepatic clearance in most of the patients with CBDS after ES, but the response to meals was individualized. Therefore, there is no need to restrict the amount of fat intake for patients who have undergone ES.

  11. Prognostic significance of blood lactate and lactate clearance in trauma patients.

    PubMed

    Régnier, Marie-Alix; Raux, Mathieu; Le Manach, Yannick; Asencio, Yves; Gaillard, Johann; Devilliers, Catherine; Langeron, Olivier; Riou, Bruno

    2012-12-01

    Lactate has been shown to be a prognostic biomarker in trauma. Although lactate clearance has already been proposed as an intermediate endpoint in randomized trials, its precise role in trauma patients remains to be determined. Blood lactate levels and lactate clearance (LC) were calculated at admission and 2 and 4 h later in trauma patients. The association of initial blood lactate level and lactate clearance with mortality was tested using receiver-operating characteristics curve, logistic regression using triage scores, Trauma Related Injury Severity Score as a reference standard, and reclassification method. The authors evaluated 586 trauma patients (mean age 38±16 yr, 84% blunt and 16% penetrating, mortality 13%). Blood lactate levels at admission were elevated in 327 (56%) patients. The lactate clearance should be calculated within the first 2 h after admission as LC0-2 h was correlated with LC0-4 h (R=0.55, P<0.001) but not with LC2-4 h (R=0.04, not significant). The lactate clearance provides additional predictive information to initial blood lactate levels and triage scores and the reference score. This additional information may be summarized using a categorical approach (i.e., less than or equal to -20 %/h) in contrast to initial blood lactate. The results were comparable in patients with high (5 mM/l or more) initial blood lactate. Early (0-2 h) lactate clearance is an important and independent prognostic variable that should probably be incorporated in future decision schemes for the resuscitation of trauma patients.

  12. HPV clearance in postpartum period of HIV-positive and negative women: a prospective follow-up study

    PubMed Central

    2013-01-01

    Background HPV persistence is a key determinant of cervical carcinogenesis. The influence of postpartum on HPV clearance has been debated. This study aimed to assess HPV clearance in later pregnancy and postpartum among HIV-positive and negative women. Methods We conducted a follow-up study with 151 HPV-positive women coinfected with HIV, in 2007–2010. After baseline assessment, all women were retested for HPV infection using PCR in later pregnancy and after delivery. Multivariable logistic regressions assessed the putative association of covariates with HPV status in between each one of the successive visits. Results Seventy-one women (47%) have eliminated HPV between the baseline visit and their second or third visits. HIV-positive women took a significantly longer time (7.0 ± 3.8 months) to clear HPV, compared to those not infected by HIV (5.9 ± 3.0 months). HPV clearance was significantly more likely to take place after delivery than during pregnancy (84.5% x 15.5%). Conclusions Both HIV-positive and negative women presented a significant reduction in HPV infection during the postpartum period. HIV-positive status was found to be associated with a longer period of time to clear HPV infection in pregnant women. PMID:24289532

  13. Determinants of urea nitrogen production in sepsis. Muscle catabolism, total parenteral nutrition, and hepatic clearance of amino acids.

    PubMed

    Pittiruti, M; Siegel, J H; Sganga, G; Coleman, B; Wiles, C E; Placko, R

    1989-03-01

    The major determinants of urea production were investigated in 26 patients with multiple trauma (300 studies). The body clearances (CLRs) of ten amino acids (AAs) were estimated as a ratio of muscle-released AAs plus total parenteral nutrition-infused AAs to their extracellular pool. While clinically septic trauma (ST) patients without multiple-organ failure syndrome (MOFS) had a higher level of urea nitrogen production (25.6 +/- 13.4 g of N per day) compared with nonseptic trauma (NST) patients (14 +/- 7.5 g of N per day) and with ST patients with MOFS (4.28 +/- 1.5 g of N per day), in all groups urea N production was found to be a function of muscle protein degradation (catabolism), total parenteral nutrition-administered AAs, and the ratio between leucine CLR and tyrosine CLR (L/T) (r2 = .82, P less than .0001). Since tyrosine is cleared almost exclusively by the liver, the L/T ratio may be regarded as an index of hepatic function. The significant differences between urea N production in ST and NST patients lay in an increased positive dependence on muscle catabolism and increased negative correlation with L/T in the ST group. At any L/T ratio, urea N production was increased in ST patients over NST patients, but in ST patients with MOFS, it fell to or below levels of NST patients. These data show that the ST process is associated with enhancement of ureagenesis, due to increased hepatic CLR of both exogenous and endogenous AAs. In sepsis with MOFS, a marked inhibition of urea synthesis occurs, partially explained by a decreased hepatic CLR of non-branched-chain AAs.

  14. Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin.

    PubMed

    Gill, Katherine L; Houston, J Brian; Galetin, Aleksandra

    2012-04-01

    Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CL(int, UGT)) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CL(int, UGT) on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CL(int, UGT) in different tissues. Although BSA increased CL(int, UGT) in all tissues, the extent was tissue- and drug-dependent. Scaled CL(int, UGT) in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min(-1) · g tissue(-1) in liver, kidney, and intestinal microsomes. Renal CL(int, UGT) (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CL(int, UGT) for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CL(int, UGT) (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CL(int, UGT) is particularly important for UGT1A9 substrates.

  15. Characterization of In Vitro Glucuronidation Clearance of a Range of Drugs in Human Kidney Microsomes: Comparison with Liver and Intestinal Glucuronidation and Impact of Albumin

    PubMed Central

    Gill, Katherine L.; Houston, J. Brian

    2012-01-01

    Previous studies have shown the importance of the addition of albumin for characterization of hepatic glucuronidation in vitro; however, no reports exist on the effects of albumin on renal or intestinal microsomal glucuronidation assays. This study characterized glucuronidation clearance (CLint, UGT) in human kidney, liver, and intestinal microsomes in the presence and absence of bovine serum albumin (BSA) for seven drugs with differential UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B7 specificity, namely, diclofenac, ezetimibe, gemfibrozil, mycophenolic acid, naloxone, propofol, and telmisartan. The impact of renal CLint, UGT on accuracy of in vitro-in vivo extrapolation (IVIVE) of glucuronidation clearance was investigated. Inclusion of 1% BSA for acidic drugs and 2% for bases/neutral drugs in incubations was found to be suitable for characterization of CLint, UGT in different tissues. Although BSA increased CLint, UGT in all tissues, the extent was tissue- and drug-dependent. Scaled CLint, UGT in the presence of BSA ranged from 2.22 to 207, 0.439 to 24.4, and 0.292 to 23.8 ml · min−1 · g tissue−1 in liver, kidney, and intestinal microsomes. Renal CLint, UGT (per gram of tissue) was up to 2-fold higher in comparison with that for liver for UGT1A9 substrates; in contrast, CLint, UGT for UGT2B7 substrates represented approximately one-third of hepatic estimates. Scaled renal CLint, UGT (in the presence of BSA) was up to 30-fold higher than intestinal glucuronidation for the drugs investigated. Use of in vitro data obtained in the presence of BSA and inclusion of renal clearance improved the IVIVE of glucuronidation clearance, with 50% of drugs predicted within 2-fold of observed values. Characterization and consideration of kidney CLint, UGT is particularly important for UGT1A9 substrates. PMID:22275465

  16. Characterization of Plasmodium Lactate Dehydrogenase and Histidine-Rich Protein 2 Clearance Patterns via Rapid On-Bead Detection from a Single Dried Blood Spot

    PubMed Central

    Markwalter, Christine F.; Gibson, Lauren E.; Mudenda, Lwiindi; Kimmel, Danielle W.; Mbambara, Saidon; Thuma, Philip E.; Wright, David W.

    2018-01-01

    Abstract. A rapid, on-bead enzyme-linked immunosorbent assay for Plasmodium lactate dehydrogenase (pLDH) and Plasmodium falciparum histidine-rich protein 2 (HRP2) was adapted for use with dried blood spot (DBS) samples. This assay detected both biomarkers from a single DBS sample with only 45 minutes of total incubation time and detection limits of 600 ± 500 pM (pLDH) and 69 ± 30 pM (HRP2), corresponding to 150 and 24 parasites/μL, respectively. This sensitive and reproducible on-bead detection method was used to quantify pLDH and HRP2 in patient DBS samples from rural Zambia collected at multiple time points after treatment. Biomarker clearance patterns relative to parasite clearance were determined; pLDH clearance followed closely with parasite clearance, whereas most patients maintained detectable levels of HRP2 for 35–52 days after treatment. Furthermore, weak-to-moderate correlations between biomarker concentration and parasite densities were found for both biomarkers. This work demonstrates the utility of the developed assay for epidemiological study and surveillance of malaria. PMID:29557342

  17. Gas turbine engine active clearance control

    NASA Technical Reports Server (NTRS)

    Deveau, Paul J. (Inventor); Greenberg, Paul B. (Inventor); Paolillo, Roger E. (Inventor)

    1985-01-01

    Method for controlling the clearance between rotating and stationary components of a gas turbine engine are disclosed. Techniques for achieving close correspondence between the radial position of rotor blade tips and the circumscribing outer air seals are disclosed. In one embodiment turbine case temperature modifying air is provided in flow rate, pressure and temperature varied as a function of engine operating condition. The modifying air is scheduled from a modulating and mixing valve supplied with dual source compressor air. One source supplies relatively low pressure, low temperature air and the other source supplies relatively high pressure, high temperature air. After the air has been used for the active clearance control (cooling the high pressure turbine case) it is then used for cooling the structure that supports the outer air seal and other high pressure turbine component parts.

  18. Foot clearance and variability in mono- and multifocal intraocular lens users during stair navigation.

    PubMed

    Renz, Erik; Hackney, Madeleine; Hall, Courtney

    2016-01-01

    Intraocular lenses (IOLs) provide distance and near refraction and are becoming the standard for cataract surgery. Multifocal glasses increase variability of toe clearance in older adults navigating stairs and increase fall risk; however, little is known about the biomechanics of stair navigation in individuals with multifocal IOLs. This study compared clearance while ascending and descending stairs in individuals with monofocal versus multifocal IOLs. Eight participants with multifocal IOLs (4 men, 4 women; mean age = 66.5 yr, standard deviation [SD] = 6.26) and fifteen male participants with monofocal IOLs (mean age = 69.9 yr, SD = 6.9) underwent vision and mobility testing. Motion analysis recorded kinematic and custom software-calculated clearances in three-dimensional space. No significant differences were found between groups on minimum clearance or variability. Clearance differed for ascending versus descending stairs: the first step onto the stair had the greatest toe clearance during ascent, whereas the final step to the floor had the greatest heel clearance during descent. This preliminary study indicates that multifocal IOLs have similar biomechanic characteristics to monofocal IOLs. Given that step characteristics are related to fall risk, we can tentatively speculate that multifocal IOLs may carry no additional fall risk.

  19. Recovery of hepatic clearance and extraction following a release of common bile duct obstruction in the rat.

    PubMed

    Melzer, E; Krepel, Z; Ronen, I; Bar-Meir, S

    1992-01-01

    The rate of recovery for hepatic clearance and extraction following release of common-duct obstruction was investigated in the rat. Male Wistar rats underwent ligation of a cannulated common bile duct. Two weeks later, the cannula was opened and implanted into the duodenum, thus re-establishing enterohepatic circulation. Hepatic extraction and indocyanine green clearance were determined in three groups of six rats each, which differed by the time elapsed from the re-establishment of communication between the common bile duct and duodenum, i.e., 1, 48 and 168 h, respectively. A fourth group, in which a sham operation was performed, served as a control. Clearance was reduced from 16.9 +/- 2.5 ml/min per kg in the control group to 2.9 +/- 0.8, 5.4 +/- 2.4, and 8.5 +/- 3.3 ml/min per kg 1, 48, and 168 h, respectively, after release of common-bile-duct obstruction. Extraction rate was reduced from 37.3 +/- 5.9% to 17.5 +/- 2.7% in the 1st hour and recovered completely at 1 week. Thus, in the rat, release of a 2-week common-bile-duct obstruction is associated with complete recovery of the extraction capacity of the liver within a week, but only incomplete recovery of clearance. This decrease in clearance seems to be due to a decrease in effective hepatic blood flow, mostly probably due to the development of porto-systemic shunts.

  20. Application of a Pharmacokinetic Model of Metformin Clearance in a Population with Acute Myeloid Leukemia

    PubMed Central

    Ceacareanu, Alice C.; Brown, Geoffrey W.; Moussa, Hoda A.; Wintrob, Zachary A. P.

    2018-01-01

    Objective: We aimed to estimate the metformin-associated lactic acidosis (MALA) risk by assessing retrospectively the renal clearance variability and applying a pharmacokinetic (PK) model of metformin clearance in a population diagnosed with acute myeloid leukemia (AML) and diabetes mellitus (DM). Methods: All adults with preexisting DM and newly diagnosed AML at Roswell Park Cancer Institute were reviewed (January 2003–December 2010, n = 78). Creatinine clearance (CrCl) and total body weight distributions were used in a two-compartment PK model adapted for multiple dosing and modified to account for actual intra- and inter-individual variability. Based on this renal function variability evidence, 1000 PK profiles were simulated for multiple metformin regimens with the resultant PK profiles being assessed for safe CrCl thresholds. Findings: Metformin 500 mg up to three times daily was safe for all simulated profiles with CrCl ≥25 mL/min. Furthermore, the estimated overall MALA risk was below 10%, remaining under 5% for 500 mg given once daily. CrCl ≥65.25 mL/min was safe for administration in any of the tested regimens (500 mg or 850 mg up to three times daily or 1000 mg up to twice daily). Conclusion: PK simulation-guided prescribing can maximize metformin's beneficial effects on cancer outcomes while minimizing MALA risk. PMID:29755998

  1. Computers in the Cop Car: Impact of the Mobile Digital Terminal Technology on Motor Vehicle Theft Clearance and Recovery Rates in a Texas City.

    ERIC Educational Resources Information Center

    Nunn, Samuel

    1993-01-01

    Assessed the impact of the Mobile Digital Terminal technology (computers used to communicate with remote crime databases) on motor vehicle theft clearance (arresting a perpetrator) and recovery rates in Fort Worth (Texas), using a time series analysis. Impact has been ambiguous, with little evidence of improved clearance or recovery. (SLD)

  2. Clearance of Apoptotic Photoreceptors

    PubMed Central

    Hisatomi, Toshio; Sakamoto, Taiji; Sonoda, Koh-hei; Tsutsumi, Chikako; Qiao, Hong; Enaida, Hiroshi; Yamanaka, Ichiro; Kubota, Toshiaki; Ishibashi, Tatsuro; Kura, Shinobu; Susin, Santos A.; Kroemer, Guido

    2003-01-01

    The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin αvβ3 revealed that phagocytotic clearance involves the PSR as well as integrin αvβ3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors are selectively eliminated via a directional process in the subretinal space. PMID:12759244

  3. Impact of mechanism vibration characteristics by joint clearance and optimization design of its multi-objective robustness

    NASA Astrophysics Data System (ADS)

    Zeng, Baoping; Wang, Chao; Zhang, Yu; Gong, Yajun; Hu, Sanbao

    2017-12-01

    Joint clearances and friction characteristics significantly influence the mechanism vibration characteristics; for example: as for joint clearances, the shaft and bearing of its clearance joint collide to bring about the dynamic normal contact force and tangential coulomb friction force while the mechanism works; thus, the whole system may vibrate; moreover, the mechanism is under contact-impact with impact force constraint from free movement under action of the above dynamic forces; in addition, the mechanism topology structure also changes. The constraint relationship between joints may be established by a repeated complex nonlinear dynamic process (idle stroke - contact-impact - elastic compression - rebound - impact relief - idle stroke movement - contact-impact). Analysis of vibration characteristics of joint parts is still a challenging open task by far. The dynamic equations for any mechanism with clearance is often a set of strong coupling, high-dimensional and complex time-varying nonlinear differential equations which are solved very difficultly. Moreover, complicated chaotic motions very sensitive to initial values in impact and vibration due to clearance let high-precision simulation and prediction of their dynamic behaviors be more difficult; on the other hand, their subsequent wearing necessarily leads to some certain fluctuation of structure clearance parameters, which acts as one primary factor for vibration of the mechanical system. A dynamic model was established to the device for opening the deepwater robot cabin door with joint clearance by utilizing the finite element method and analysis was carried out to its vibration characteristics in this study. Moreover, its response model was carried out by utilizing the DOE method and then the robust optimization design was performed to sizes of the joint clearance and the friction coefficient change range so that the optimization design results may be regarded as reference data for selecting bearings

  4. Traffic incident management quick clearance laws : a national review of best practices.

    DOT National Transportation Integrated Search

    2008-12-01

    Constituting Quick Clearance Laws, three types of general legislation Move Over, Driver Removal, and Authority Removal laws - support concurrent Quick Clearance operations intended to enhance motorist and responder safety, as well as reduce...

  5. Physiological stability and renal clearance of ultrasmall zwitterionic gold nanoparticles: Ligand length matters

    NASA Astrophysics Data System (ADS)

    Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, Rodrigo D.; Yu, Mengxiao; Zheng, Jie

    2017-05-01

    Efficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.

  6. Design optimization of dual-axis driving mechanism for satellite antenna with two planar revolute clearance joints

    NASA Astrophysics Data System (ADS)

    Bai, Zheng Feng; Zhao, Ji Jun; Chen, Jun; Zhao, Yang

    2018-03-01

    In the dynamic analysis of satellite antenna dual-axis driving mechanism, it is usually assumed that the joints are ideal or perfect without clearances. However, in reality, clearances in joints are unavoidable due to assemblage, manufacturing errors and wear. When clearance is introduced to the mechanism, it will lead to poor dynamic performances and undesirable vibrations due to impact forces in clearance joint. In this paper, a design optimization method is presented to reduce the undesirable vibrations of satellite antenna considering clearance joints in dual-axis driving mechanism. The contact force model in clearance joint is established using a nonlinear spring-damper model and the friction effect is considered using a modified Coulomb friction model. Firstly, the effects of clearances on dynamic responses of satellite antenna are investigated. Then the optimization method for dynamic design of the dual-axis driving mechanism with clearance is presented. The objective of the optimization is to minimize the maximum absolute vibration peak of antenna acceleration by reducing the impact forces in clearance joint. The main consideration here is to optimize the contact parameters of the joint elements. The contact stiffness coefficient, damping coefficient and the dynamic friction coefficient for clearance joint elements are taken as the optimization variables. A Generalized Reduced Gradient (GRG) algorithm is used to solve this highly nonlinear optimization problem for dual-axis driving mechanism with clearance joints. The results show that the acceleration peaks of satellite antenna and contact forces in clearance joints are reduced obviously after design optimization, which contributes to a better performance of the satellite antenna. Also, the application and limitation of the proposed optimization method are discussed.

  7. Test Rig for Active Turbine Blade Tip Clearance Control Concepts: An Update

    NASA Technical Reports Server (NTRS)

    Taylor, Shawn; Steinetz, Bruce; Oswald, Jay; DeCastro, Jonathan; Melcher, Kevin

    2006-01-01

    The objective is to develop and demonstrate a fast-acting active clearance control system to improve turbine engine performance, reduce emissions, and increase service life. System studies have shown the benefits of reducing blade tip clearances in modern turbine engines. Minimizing blade tip clearances throughout the engine will contribute materially to meeting NASA's Ultra-Efficient Engine Technology (UEET) turbine engine project goals. NASA GRC is examining two candidate approaches including rub-avoidance and regeneration which are explained in subsequent slides.

  8. Increased Glyburide Clearance in the Pregnant Mouse Model

    PubMed Central

    Zhou, Lin; Zhang, Yi; Hebert, Mary F.; Unadkat, Jashvant D.

    2010-01-01

    Glyburide (GLB) is an oral sulfonylurea, commonly used for the treatment of gestational diabetes mellitus. It has been reported that the clearance of GLB in pregnant women is significantly higher than that in nonpregnant women. The molecular mechanism by which pregnancy increases the clearance of GLB is not known, but it may be caused by increased CYP3A activity. Because liver tissue from pregnant women is not readily available, in the present study, we investigated the mechanism of such pregnancy-related changes in GLB disposition in a mouse model. We demonstrated that the systemic clearance of GLB in pregnant mice was increased approximately 2-fold (p < 0.01) compared with nonpregnant mice, a magnitude of change similar to that observed in the clinical study. Plasma protein binding of GLB in mice was not altered by pregnancy. The half-life of GLB depletion in hepatic S-9 fractions of pregnant mice was significantly shorter than that of nonpregnant mice. Moreover, GLB depletion was markedly inhibited by ketoconazole, a potent inhibitor of mouse Cyp3a, suggesting that GLB metabolism in mice is primarily mediated by hepatic Cyp3a. These data suggest that the increased systemic clearance of GLB in pregnant mice is likely caused by an increase in hepatic Cyp3a activity during pregnancy, and they provide a basis for further mechanistic understanding and analysis of pregnancy-induced alterations in the disposition of GLB and drugs that are predominantly and extensively metabolized by CYP3A/Cyp3a. PMID:20558597

  9. Impaired lipid clearance in patients with previous acute pancreatitis.

    PubMed Central

    Guzmán, S; Nervi, F; Llanos, O; León, P; Valdivieso, V

    1985-01-01

    Fasting serum triglycerides were measured in 52 patients who had sustained an attack of pancreatitis (gall stone related 33, alcoholism six) at least six months earlier. Several patients (23%) had raised fasting serum triglycerides, with a type IV phenotype in all but one patient. The 40 patients with normal fasting serum triglycerides received an oral load of 100 g sunflower oil to compare their clearance of dietary triglycerides with that of a control group of 54 subjects. The clearance of ingested triglycerides was significantly impaired in the patients - irrespective of the presumed aetiological factor, or clinical condition associated with pancreatitis - compared with the clearance in controls. A triglyceride tolerance test is the only way to detect those patients in whom a future attack of pancreatitis may be precipitated by a diet rich in fat, or endogenous over production of triglycerides as after an alcoholic debauch. PMID:4029716

  10. Mineral water administration may increase kidney elimination of urea, creatinine and folic acid in a concentration-dependent fashion.

    PubMed

    Calomino, Francesco; Di Paolo, Nicola; Nicolai, Giulia; Miglio, Antonio

    2010-05-01

    In a previous experimental study we showed that the administration of a large water load in a short time increases the urinary flow and the transport capacity in the excretory tract of the rabbit ureter. In human subjects drinking a water load of 25 ml/kg(BW) in 30 minutes, diuresis, creatinine and urea clearance increase more than in those drinking the same load in 24 hours. The aim of the present study was to investigate possible correlations between percent reduction and baseline values of serum urea, creatinine, folic acid, and magnesium in humans. 20 volunteers were divided in two groups. Subjects in group 1 received a water load of 25 ml/kg(BW) in 24 hours followed by the same load in 30 minutes. Subjects in group 2 received the same water load but in inverse order. Before and after each water administration, the following variables were measured and compared: diuresis, serum urea, creatinine, folic acid and magnesium concentration, and urea and creatinine clearance. Serum urea and folic acid concentration decreased up to 40% after administration of the water load in 24 hours. Serum creatinine concentration decreased up to 20% after administration of the water load in 30 minutes. The concentration drop of these metabolites increased with increasing baseline metabolite concentrations.

  11. Ghrelin clearance is reduced at the late stage of polymicrobial sepsis.

    PubMed

    Wu, Rongqian; Zhou, Mian; Cui, Xiaoxuan; Simms, H Hank; Wang, Ping

    2003-11-01

    The cardiovascular response to sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Ghrelin, a newly-identified endogenous ligand for growth hormone secretagogue receptor (i.e., ghrelin receptor), was recently demonstrated to be a potent vasoactive peptide in addition to its effects on growth hormone release and energy homeostasis. We have shown that ghrelin (via its receptor) may play an important role in regulating cardiovascular responses in the progression of polymicrobial sepsis. However, it remains unknown whether the clearance of this peptide is altered in sepsis. To determine this, male adult rats were injected with 125I-ghrelin through the jugular vein at 5 or 20 h after cecal ligation and puncture (CLP, i.e., sepsis model) or sham operation. The blood sample was collected every 2 min for 30 min for determining half-life (t1/2). Tissue samples (i.e., kidneys, liver, brain, heart, lungs, spleen, stomach, small intestine, large intestine, skin and muscle) were then harvested. The radioactivities of samples were counted. The results indicate that 125I-ghrelin's t1/2 and its distribution were not significantly altered in early sepsis (5 h after CLP). However, the t1/2 increased significantly in late sepsis (20 h after CLP). Tissue distribution of 125I-ghrelin was far greater in the kidneys than in any other tissues tested in both sham and septic animals. Moreover, the kidneys and liver had significantly less radioactive uptake at 20 h after CLP, but the radioactivity in blood was much higher at the same time point. There were no significant changes in 125I-ghrelin distribution in other organs at the late stage of sepsis. These results indicate that the kidneys are the primary site of ghrelin clearance, which is significantly diminished in late sepsis. In addition, the liver also plays a role in the clearance of ghrelin, which was also reduced in late sepsis. The decreased clearance of ghrelin by the kidneys and liver

  12. Participation of the hypophyseal-adrenal cortex system in thrombin clearance during immobilization stress

    NASA Technical Reports Server (NTRS)

    Kudryashov, B. A.; Uljanov, A. M.; Shapiro, F. B.; Bazazyan, G. G.

    1981-01-01

    Thrombin marked with I-131 resulted in a considerable increase of the thrombined clearance rate in healthy male rats during stress caused by an immobilization lasting 30 minutes, and in an increase of thrombin clearance occurred by a combination of immobilization and administration of adrenocorticotropin (ACTH). Contrary to ACTH, the thrombin clearance is not stimulated in healthy animals by hydrocortisone. The results of the examination are presented.

  13. Effects of nitrogen dioxide on respiratory tract clearance in the ferret

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rasmussen, R.E.; Mannix, R.C.; Oldham, M.J.

    1994-01-01

    During growth and development, young children are periodically exposed to relatively high concentrations of various air contaminants, including tobacco smoke and environmental pollutants generated by fossil fuel use. The effects of these exposures on respiratory function and lung development are difficult to determine because of interindividual variation and lack of accurate dosimetry. To provide information on the effects of chronic exposure to a common indoor and outdoor pollutant during lung development, a study was performed to assess the effects of exposure to two concentrations of nitrogen dioxide (NO[sub 2]; 0.5 or 10 ppm) on tracer particle clearance from the airwaysmore » of ferrets exposed during postnatal respiratory tract development. Separate groups of ferrets were exposed nose-only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15 wk. Those animals exposed for 8 wk were subsequently housed in a filtered air environment until the particle clearance measurements commenced at 3 wk prior to the end of the 15-wk exposure protocol. Radiolabeled ([sup 51]Cr) tracer particles were deposited in the respiratory tract of all animals by inhalation, and the clearance rates from the head and thoracic regions were separately monitored for 18 d. No significant effects of the NO[sub 2] exposure on head airways clearance were seen. In contrast, the rates of particle clearance from the thorax of both the 8- and 15-wk groups exposed to 10 ppm NO[sub 2] were significantly reduced, and did not differ from each other. Thoracic clearance was also reduced in animals exposed to 0.5 ppm, but the rate was not significantly different from that of the clean air exposed controls. These results show that NO[sub 2] at moderate concentrations caused highly significant changes in the deep lung of the juvenile ferret, and suggest that impairment of the clearance function may be only slowly recovered after chronic exposure. 35 refs., 1 fig., 1 tab.« less

  14. The description of a method for accurately estimating creatinine clearance in acute kidney injury.

    PubMed

    Mellas, John

    2016-05-01

    Acute kidney injury (AKI) is a common and serious condition encountered in hospitalized patients. The severity of kidney injury is defined by the RIFLE, AKIN, and KDIGO criteria which attempt to establish the degree of renal impairment. The KDIGO guidelines state that the creatinine clearance should be measured whenever possible in AKI and that the serum creatinine concentration and creatinine clearance remain the best clinical indicators of renal function. Neither the RIFLE, AKIN, nor KDIGO criteria estimate actual creatinine clearance. Furthermore there are no accepted methods for accurately estimating creatinine clearance (K) in AKI. The present study describes a unique method for estimating K in AKI using urine creatinine excretion over an established time interval (E), an estimate of creatinine production over the same time interval (P), and the estimated static glomerular filtration rate (sGFR), at time zero, utilizing the CKD-EPI formula. Using these variables estimated creatinine clearance (Ke)=E/P * sGFR. The method was tested for validity using simulated patients where actual creatinine clearance (Ka) was compared to Ke in several patients, both male and female, and of various ages, body weights, and degrees of renal impairment. These measurements were made at several serum creatinine concentrations in an attempt to determine the accuracy of this method in the non-steady state. In addition E/P and Ke was calculated in hospitalized patients, with AKI, and seen in nephrology consultation by the author. In these patients the accuracy of the method was determined by looking at the following metrics; E/P>1, E/P<1, E=P in an attempt to predict progressive azotemia, recovering azotemia, or stabilization in the level of azotemia respectively. In addition it was determined whether Ke<10 ml/min agreed with Ka and whether patients with AKI on renal replacement therapy could safely terminate dialysis if Ke was greater than 5 ml/min. In the simulated patients there

  15. Reticuloendothelial clearance of blood-borne particulates: relevance to experimental lung microembolization and vascular injury.

    PubMed

    Niehaus, G D; Schumacker, P R; Saba, T M

    1980-04-01

    The rapid increase in sheep lung vascular permeability observed during Pseudomonas aeruginosa bacteremia may be due to embolization of the pulmonary microvasculature by bloodborne particulates. Since alterations in lung microvascular permeability during mild septicemia in sheep may reflect inefficient RES phagocytic clearance of bacteria as well as products of bacterial induced intravascular coagulation, the opsonic and phagocytic aspects of RES function in sheep (30-50 kg) were compared to other species. RES function was evaluated by both the clearance and relative organ uptake of gelatinized I(131) RE test lipid emulsion and gelatinized colloidal carbon. Immunoreactive opsonic a(2)SB glycoprotein levels were determined by electroimmunoassay. The phagocytic index for RES clearance of the gelatinized (500 mg/kg) test lipid in sheep was 0.019 +/- 0.002 corresponding to a half-time of 16.65 +/- 1.74 minutes. With colloidal carbon (64 mg/kg), the phagocytic index in sheep was 0.080 +/- 0.026, corresponding to a half-time of 6.16 +/- 1.99 minutes. The per cent of injected lipid emulsion (%ID) in major RE organs, on a total organ basis (TO), was: liver = 15.69 +/- 1.65%; spleen = 2.09 +/- 0.78%. Localization in the lung = 31.39 +/- 6.2%. The per cent of carbon localized in major RE organs (%ID/TO) was: liver = 21.37 +/- 1.9%; spleen = 1.95 +/- 0.55%. Localization in the lung = 32.70 +/- 4.55%. In contrast, clearance and organ distribution of the blood-borne test microparticles in rats and dogs at the same relative challenging dose revealed a much more intense and rapid liver and spleen RES uptake with minimal lung localization (1-2%). Immunoreactive opsonic protein concentrations varied greatly with species and directly correlated with efficiency of RES function. Levels observed were: dog = 1285 +/- 135 microg/ml; mouse = 1077 +/- 67 microg/ml; rat = 400 +/- 31 microg/ml; human = 297 +/- 10 microg/ml; and sheep = 184 +/- 13 microg/ml. After intravenous particulate

  16. Lactate clearance cut off for early mortality prediction in adult sepsis and septic shock patients

    NASA Astrophysics Data System (ADS)

    Sinto, R.; Widodo, D.; Pohan, H. T.

    2018-03-01

    Previous lactate clearance cut off for early mortality prediction in sepsis and septic shock patient was determined by consensus from small sample size-study. We investigated the best lactate clearance cut off and its ability to predict early mortality in sepsis and septic shock patients. This cohort study was conducted in Intensive Care Unit of CiptoMangunkusumo Hospital in 2013. Patients’ lactate clearance and eight other resuscitationendpoints were recorded, and theoutcome was observed during the first 120 hours. The clearance cut off was determined using receiver operating characteristic (ROC) analysis, and its ability was investigated with Cox’s proportional hazard regression analysis using other resuscitation endpoints as confounders. Total of 268 subjects was included, of whom 70 (26.11%) subjects died within the first 120 hours. The area under ROC of lactate clearance to predict early mortality was 0.78 (95% % confidence interval [CI] 0.71-0.84) with best cut off was <7.5% (sensitivity and specificity 88.99% and 81.4% respectively). Compared with group achieving lactate clearance target, group not achieving lactate clearance target had to increase early mortality risk (adjusted hazard ratio 13.42; 95%CI 7.19-25.07). In conclusion, the best lactate clearance cut off as anearly mortality predictor in sepsis and septic shock patients is 7.5%.

  17. Wear in ceramic on ceramic type lumbar total disc replacement: effect of radial clearance.

    PubMed

    Shankar, S; Kesavan, D

    2015-01-01

    The wear of the bearing surfaces of total disc replacement (TDR) is a key problem leads to reduction in the lifetime of the prosthesis and it mainly occurs due to the range of clearances of the articulating surface between the superior plate and core. The objective of this paper is to estimate the wear using finite element concepts considering the different radial clearances between the articulating surfaces of ceramic on ceramic type Lumbar Total Disc Replacement (LTDR). The finite element (FE) model was subjected to wear testing protocols according to loading profile of International Standards Organization (ISO) 18192 standards through 10 million cycles. The radial clearance value of 0.05 mm showed less volumetric wear when compared with other radial clearance values. Hence, low radial clearance values are suitable for LTDR to minimize the wear.

  18. Capacitance-type blade-tip clearance measurement system using a dual amplifier with ramp/dc inputs and integration

    NASA Technical Reports Server (NTRS)

    Sarma, Garimella R.; Barranger, John P.

    1992-01-01

    The analysis and prototype results of a dual-amplifier circuit for measuring blade-tip clearance in turbine engines are presented. The capacitance between the blade tip and mounted capacitance electrode within a guard ring of a probe forms one of the feedback elements of an operational amplifier (op amp). The differential equation governing the circuit taking into consideration the nonideal features of the op amp was formulated and solved for two types of inputs (ramp and dc) that are of interest for the application. Under certain time-dependent constraints, it is shown that (1) with a ramp input the circuit has an output voltage proportional to the static tip clearance capacitance, and (2) with a dc input, the output is proportional to the derivative of the clearance capacitance, and subsequent integration recovers the dynamic capacitance. The technique accommodates long cable lengths and environmentally induced changes in cable and probe parameters. System implementation for both static and dynamic measurements having the same high sensitivity is also presented.

  19. Capacitance-type blade-tip clearance measurement system using a dual amplifier with ramp/dc inputs and integration

    NASA Astrophysics Data System (ADS)

    Sarma, Garimella R.; Barranger, John P.

    1992-10-01

    The analysis and prototype results of a dual-amplifier circuit for measuring blade-tip clearance in turbine engines are presented. The capacitance between the blade tip and mounted capacitance electrode within a guard ring of a probe forms one of the feedback elements of an operational amplifier (op amp). The differential equation governing the circuit taking into consideration the nonideal features of the op amp was formulated and solved for two types of inputs (ramp and dc) that are of interest for the application. Under certain time-dependent constraints, it is shown that (1) with a ramp input the circuit has an output voltage proportional to the static tip clearance capacitance, and (2) with a dc input, the output is proportional to the derivative of the clearance capacitance, and subsequent integration recovers the dynamic capacitance. The technique accommodates long cable lengths and environmentally induced changes in cable and probe parameters. System implementation for both static and dynamic measurements having the same high sensitivity is also presented.

  20. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

  1. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

  2. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

  3. 28 CFR 524.74 - Activities clearance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., AND TRANSFER CLASSIFICATION OF INMATES Central Inmate Monitoring (CIM) System § 524.74 Activities... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Activities clearance. 524.74 Section 524... authority on all transfers, temporary releases, community activities, and escorted trips. (b) Witness...

  4. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL...

  5. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL...

  6. 15 CFR 752.15 - Export clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Export clearance. 752.15 Section 752.15 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS SPECIAL...

  7. 20 CFR 653.501 - Requirements for accepting and processing clearance orders.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Agricultural Clearance Order Activity § 653.501... function of the job service as a no-fee labor exchange, that is, as a forum for bringing together employers... referred through the clearance system shall be notified to contact a local job service office, preferably...

  8. 20 CFR 653.501 - Requirements for accepting and processing clearance orders.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., DEPARTMENT OF LABOR SERVICES OF THE EMPLOYMENT SERVICE SYSTEM Agricultural Clearance Order Activity § 653.501... function of the job service as a no-fee labor exchange, that is, as a forum for bringing together employers... referred through the clearance system shall be notified to contact a local job service office, preferably...

  9. Quantifying salinity and season effects on eastern oyster clearance and oxygen consumption rates

    USGS Publications Warehouse

    Casas, S.M.; Lavaud, Romain; LaPeyre, Megan K.; Comeau, L. A.; Filgueira, R.; LaPeyre, Jerome F.

    2018-01-01

    There are few data on Crassostrea virginica physiological rates across the range of salinities and temperatures to which they are regularly exposed, and this limits the applicability of growth and production models using these data. The objectives of this study were to quantify, in winter (17 °C) and summer (27 °C), the clearance and oxygen consumption rates of C. virginica from Louisiana across a range of salinities typical of the region (3, 6, 9, 15 and 25). Salinity and season (temperature and reproduction) affected C. virginica physiology differently; salinity impacted clearance rates with reduced feeding rates at low salinities, while season had a strong effect on respiration rates. Highest clearance rates were found at salinities of 9–25, with reductions ranging from 50 to 80 and 90 to 95% at salinities of 6 and 3, respectively. Oxygen consumption rates in summer were four times higher than in winter. Oxygen consumption rates were within a narrow range and similar among salinities in winter, but varied greatly among individuals and salinities in summer. This likely reflected varying stages of gonad development. Valve movements measured at the five salinities indicated oysters were open 50–60% of the time in the 6–25 salinity range and ~ 30% at a salinity of 3. Reduced opening periods, concomitant with narrower valve gap amplitudes, are in accord with the limited feeding at the lowest salinity (3). These data indicate the need for increased focus on experimental determination of optimal ranges and thresholds to better quantify oyster population responses to environmental changes.

  10. Real time non invasive imaging of fatty acid uptake in vivo

    PubMed Central

    Henkin, Amy H.; Cohen, Allison S.; Dubikovskaya, Elena A.; Park, Hyo Min; Nikitin, Gennady F.; Auzias, Mathieu G.; Kazantzis, Melissa; Bertozzi, Carolyn R.; Stahl, Andreas

    2012-01-01

    Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin-sensitivity. To enable non-invasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real-time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models. PMID:22928772

  11. Enoxacin decreases the clearance of theophylline in man.

    PubMed Central

    Wijnands, W J; Vree, T B; Van Herwaarden, C L

    1985-01-01

    In patients treated concurrently with theophylline and enoxacin, a new broad-spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured. In part I of this study, daily plasma theophylline concentrations were measured in 14 patients. The mean +/- s.d. theophylline concentrations increased from 8.5 +/- 2.8 micrograms ml-1 prior to enoxacin to a maximum of 21.7 +/- 7.8 micrograms ml-1 during coadministration. In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions. Plasma theophylline concentrations rose from 8.4 +/- 2.4 micrograms ml-1 prior to enoxacin treatment to 15.0 +/- 5.1 micrograms ml-1 at day 3 of coadministration (P less than 0.005). Plasma protein-binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005). From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline. If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended. PMID:3867394

  12. Lactate clearance as the predictor of outcome in pediatric septic shock.

    PubMed

    Choudhary, Richa; Sitaraman, Sadasivan; Choudhary, Anita

    2017-01-01

    Septic shock can rapidly evolve into multiple system organ failure and death. In the recent years, hyperlactatemia has been found to be a risk factor for mortality in critically ill adults. To evaluate the predictive value of lactate clearance and to determine the optimal cut-off value for predicting outcome in children with septic shock. A prospective observational study was performed on children with septic shock admitted to pediatric Intensive Care Unit (PICU). Serial lactate levels were measured at PICU admission, 24 and 48 h later. Lactate clearance, percent decrease in lactate level in 24 h, was calculated. The primary outcome measure was survival or nonsurvival at the end of hospital stay. We performed receiver operating characteristic analyses to calculate optimal cut-off values. The mean lactate levels at admission were significantly higher in the nonsurvivors than survivors, 5.12 ± 3.51 versus 3.13 ± 1.71 mmol/L ( P = 0.0001). The cut-off for lactate level at admission for the best prediction of mortality was determined as ≥4 mmol/L (odds ratio 5.4; 95% confidence interval [CI] =2.45-12.09). Mean lactate clearance was significantly higher in survivors than nonsurvivors (17.9 ± 39.9 vs. -23.2 ± 62.7; P < 0.0001). A lactate clearance rate of <10% at 24 h had a sensitivity and specificity of 78.7% and 72.2%, respectively and a positive predictive value of 83.1% for death. Failure to achieve a lactate clearance of more than 10% was associated with greater risk of mortality (likelihood ratio + 2.83; 95% CI = 1.82-4.41). Serial lactate levels can be used to predict outcome in pediatric septic shock. A 24 h lactate clearance cut-off of <10% is a predictor of in-hospital mortality in such patients.

  13. 14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

  14. 14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

  15. 14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

  16. 14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

  17. 14 CFR 105.17 - Flight visibility and clearance from cloud requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Flight visibility and clearance from cloud... Flight visibility and clearance from cloud requirements. No person may conduct a parachute operation, and...— (a) Into or through a cloud, or (b) When the flight visibility or the distance from any cloud is less...

  18. Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates.

    PubMed

    De Cock, Roosmarijn F W; Allegaert, Karel; Vanhaesebrouck, Sophie; de Hoon, Jan; Verbesselt, Rene; Danhof, Meindert; Knibbe, Catherijne A J

    2014-06-01

    Despite limited information being available on the pharmacokinetics of excipients, propylene glycol (PG) is often used as an excipient in both adults and children. The aim of this study is to characterize the renal and hepatic elimination of PG in preterm and term neonates. The pharmacokinetic analysis of PG was performed in NONMEM 6.2. on the basis of PG concentrations in plasma and/or urine samples for a total of 69 (pre)term neonates (birth weight 630-3980 g, gestational age 24-41 weeks, postnatal age 1-29 days) who received PG coadministered with intravenous paracetamol (5-10 mg/kg per 6 hours), phenobarbital (5 mg·kg(-1)·d(-1)), or both. To capture the time-dependent trend in the renal excretion of PG, different models based on time after the first dose, urine volume, and creatinine amount in urine were tested. A one-compartment model parameterized in terms of renal clearance, hepatic clearance, and volume of distribution was found to adequately describe the observations in both plasma and urine. After the first dose was administered, the renal elimination of PG was 15% of total clearance, which increased over time to 25% at 24 hours after the first dose of PG. This increase was best described using a hyperbolic function based on time after the first dose. Renal elimination of PG in (pre)term neonates is low, particularly compared with the reported percentage of 45% in adults, but it may increase with time after the first dose of PG. To study whether this increase is caused by an autoinduced increase in the renal secretion or a reduction of tubular reabsorption of PG, further research is needed.

  19. Timing of dornase alfa inhalation for cystic fibrosis.

    PubMed

    Dentice, Ruth; Elkins, Mark

    2016-07-26

    Inhalation of the enzyme dornase alfa reduces sputum viscosity and improves clinical outcomes of people with cystic fibrosis. This is an update of a previously published Cochrane review. To determine the effect of timing of dornase alfa inhalation on measures of clinical efficacy in people with cystic fibrosis (in relation to airway clearance techniques or time of day). Relevant randomised and quasi-randomised controlled trials were identified from the Cochrane Cystic Fibrosis Trials Register, Physiotherapy Evidence Database (PEDro), and international cystic fibrosis conference proceedings.Date of the most recent search: 25 April 2016. Any trial of dornase alfa in people with cystic fibrosis where timing of inhalation was the randomised element in the study with either: inhalation before compared to after airway clearance techniques; or morning compared to evening inhalation. Both authors independently selected trials, assessed risk of bias and extracted data with disagreements resolved by discussion. Relevant data were extracted and, where possible, meta-analysed. We identified 115 trial reports representing 55 studies, of which five studies (providing data on 122 participants) met our inclusion criteria. All five studies used a cross-over design. Intervention periods ranged from two to eight weeks. Four trials compared dornase alfa inhalation before versus after airway clearance techniques. Inhalation after instead of before airway clearance did not significantly change forced expiratory volume at one second. Similarly, forced vital capacity and quality of life were not significantly affected; forced expiratory flow at 25% was significantly worse with dornase alfa inhalation after airway clearance, mean difference -0.17 litres (95% confidence interval -0.28 to -0.05), based on the pooled data from two small studies in children (seven to 19 years) with well-preserved lung function. All other secondary outcomes were statistically non-significant.In one trial

  20. Structural Health Monitoring on Turbine Engines Using Microwave Blade Tip Clearance Sensors

    NASA Technical Reports Server (NTRS)

    Woike, Mark; Abdul-Aziz, Ali; Clem, Michelle

    2014-01-01

    The ability to monitor the structural health of the rotating components, especially in the hot sections of turbine engines, is of major interest to aero community in improving engine safety and reliability. The use of instrumentation for these applications remains very challenging. It requires sensors and techniques that are highly accurate, are able to operate in a high temperature environment, and can detect minute changes and hidden flaws before catastrophic events occur. The National Aeronautics and Space Administration (NASA) has taken a lead role in the investigation of new sensor technologies and techniques for the in situ structural health monitoring of gas turbine engines. As part of this effort, microwave sensor technology has been investigated as a means of making high temperature non-contact blade tip clearance, blade tip timing, and blade vibration measurements for use in gas turbine engines. This paper presents a summary of key results and findings obtained from the evaluation of two different types of microwave sensors that have been investigated for use possible in structural health monitoring applications. The first is a microwave blade tip clearance sensor that has been evaluated on a large scale Axial Vane Fan, a subscale Turbofan, and more recently on sub-scale turbine engine like disks. The second is a novel microwave based blade vibration sensor that was also used in parallel with the microwave blade tip clearance sensors on the experiments with the sub-scale turbine engine disks.

  1. Structural health monitoring on turbine engines using microwave blade tip clearance sensors

    NASA Astrophysics Data System (ADS)

    Woike, Mark; Abdul-Aziz, Ali; Clem, Michelle

    2014-04-01

    The ability to monitor the structural health of the rotating components, especially in the hot sections of turbine engines, is of major interest to the aero community in improving engine safety and reliability. The use of instrumentation for these applications remains very challenging. It requires sensors and techniques that are highly accurate, are able to operate in a high temperature environment, and can detect minute changes and hidden flaws before catastrophic events occur. The National Aeronautics and Space Administration (NASA) has taken a lead role in the investigation of new sensor technologies and techniques for the in situ structural health monitoring of gas turbine engines. As part of this effort, microwave sensor technology has been investigated as a means of making high temperature non-contact blade tip clearance, blade tip timing, and blade vibration measurements for use in gas turbine engines. This paper presents a summary of key results and findings obtained from the evaluation of two different types of microwave sensors that have been investigated for possible use in structural health monitoring applications. The first is a microwave blade tip clearance sensor that has been evaluated on a large scale Axial Vane Fan, a subscale Turbofan, and more recently on sub-scale turbine engine like disks. The second is a novel microwave based blade vibration sensor that was also used in parallel with the microwave blade tip clearance sensors on the same experiments with the sub-scale turbine engine disks.

  2. Transitional probability-based model for HPV clearance in HIV-1-positive adolescent females.

    PubMed

    Kravchenko, Julia; Akushevich, Igor; Sudenga, Staci L; Wilson, Craig M; Levitan, Emily B; Shrestha, Sadeep

    2012-01-01

    HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals). Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm(3), p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm(3)). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection. This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related

  3. 10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL SECURITY INFORMATION OR AN EMPLOYMENT CLEARANCE... access authorization and/or an employment clearance, the Director, Division of Facilities and Security... Corporate Management and Chief Information Officer or other Deputy Executive Director, his or her...

  4. 10 CFR 10.21 - Suspension of access authorization and/or employment clearance.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ELIGIBILITY FOR ACCESS TO RESTRICTED DATA OR NATIONAL SECURITY INFORMATION OR AN EMPLOYMENT CLEARANCE... access authorization and/or an employment clearance, the Director, Division of Facilities and Security... Corporate Management and Chief Information Officer or other Deputy Executive Director, his or her...

  5. Morphine clearance in children: does race or genetics matter?

    PubMed

    Sadhasivam, Senthilkumar; Krekels, Elke H J; Chidambaran, Vidya; Esslinger, Hope R; Ngamprasertwong, Pornswan; Zhang, Kejian; Fukuda, Tsuyoshi; Vinks, Alexander A

    2012-01-01

    Interindividual variability in analgesic response and adverse effects of opioids because of narrow therapeutic indices are major clinical problems. Morphine is an opioid commonly used in children to manage perioperative pain. Al-though size and age often are considered primary covariates for morphine pharmacokinetic models, the impact of other factors important in personalizing care such as race and genetic variations on morphine disposition is not well documented. Genotype blinded clinical observational pharmacokinetic study. One hundred forty-six African American and Caucasian children scheduled for elective outpatient adenotonsillectomy were enrolled in our prospective genotype blinded observational study with standard perioperative clinical care. Tertiary care pediatric institution. Morphine bolus for intraoperative analgesia in children and pharmacokinetic analyses in different races. Pharmacokinetics and pharmacogenetics of intravenous morphine in a homogeneous pediatric outpatient surgical pain population were evaluated. The authors observed that African American children have higher morphine clearance than Caucasian children. The increased clearance is directed toward the formation of morphine-3-glucuronide formation, rather than the formation of morphine-6-glucuronide. Common uridine diphosphate glucuronosyl transferase (UGT) 2B7 genetic variations (2161C>T and 802C>T) were not associated with observed racial differences in morphine's clearance although the wild type of the UGT2B7 isozyme is more prevalent in the African Americans. Race of the child is an important factor in perioperative intravenous morphine's clearance and its potential role in personalizing analgesia with morphine needs further investigation.

  6. Dual roles for hepatic lectin receptors in the clearance of chilled platelets.

    PubMed

    Rumjantseva, Viktoria; Grewal, Prabhjit K; Wandall, Hans H; Josefsson, Emma C; Sørensen, Anne Louise; Larson, Göran; Marth, Jamey D; Hartwig, John H; Hoffmeister, Karin M

    2009-11-01

    Rapid chilling causes glycoprotein-Ib (GPIb) receptors to cluster on blood platelets. Hepatic macrophage beta(2) integrin binding to beta-N-acetylglucosamine (beta-GlcNAc) residues in the clusters leads to rapid clearance of acutely chilled platelets after transfusion. Although capping the beta-GlcNAc moieties by galactosylation prevents clearance of short-term-cooled platelets, this strategy is ineffective after prolonged refrigeration. We report here that prolonged refrigeration increased the density and concentration of exposed galactose residues on platelets such that hepatocytes, through Ashwell-Morell receptor binding, become increasingly involved in platelet removal. Macrophages rapidly removed a large fraction of transfused platelets independent of their storage conditions. With prolonged platelet chilling, hepatocyte-dependent clearance further diminishes platelet recovery and survival after transfusion. Inhibition of chilled platelet clearance by both beta(2) integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold.

  7. A prototype wireless inertial-sensing device for measuring toe clearance.

    PubMed

    Lai, Daniel T H; Charry, E; Begg, R; Palaniswami, M

    2008-01-01

    Tripping and slipping are serious health concerns for the elderly because they result in life threatening injuries i.e., fractures and high medical costs. Our recent work in detection of tripping gait patterns has demonstrated that minimum toe clearance (MTC) is a sensitive falls risk predictor. MTC measurement has previously been done in gait laboratories and on treadmills which potentially imposes controlled walking conditions. In this paper, we describe a prototype design of a wireless device for monitoring vertical toe clearance. The sensors consists of a tri-axis accelerometer and dual-axis gyroscope connected to Crossbow sensor motes for wireless data transmission. Sensor data are transmitted to a laptop and displayed on a Matlab graphic user interface (GUI). We have performed zero base and treadmill experiments to investigate sensor performance to environmental variations and compared the calculated toe clearance against measurements made by an Optotrak motion system. It was found that device outputs were approximately independent of small ambient temperature variations, had a reliable range of 20m indoors and 50m outdoors and a maximum transmission rate of 20 packets/s. Toe clearance measurements were found to follow the Optotrak measurement trend but could be improved further by dealing with double integration errors and improving data transmission rates.

  8. Deposition, retention, and clearance of inhaled particles.

    PubMed Central

    Lippmann, M; Yeates, D B; Albert, R E

    1980-01-01

    The relation between the concentrations and characteristics of air contaminants in the work place and the resultant toxic doses and potential hazards after their inhalation depends greatly on their patterns of deposition and the rates and pathways for their clearance from the deposition sites. The distribution of the deposition sites of inhaled particles is strongly dependent on their aerodynamic diameters. For normal man, inhaled non-hygroscopic particles greater than or equal to 2 micrometers that deposit in the conducting airways by impaction are concentrated on to a small fraction of the surface. Cigarette smoking and bronchitis produce a proximal shift in the deposition pattern. The major factor affecting the deposition of smaller particles is their transfer from tidal to reserve air. For particles soluble in respiratory tract fluid, systemic uptake may be relatively complete for all deposition patterns, and there may be local toxic or irritant effects or both. On the other hand, slowly soluble particles depositing in the conducting airways are carried on the surface to the glottis and are swallowed within one day. Mucociliary transport rates are highly variable, both along the ciliated airways of a given individual and between individuals. The changes in clearance rates produced by drugs, cigarette smoke, and other environmental pollutants can greatly increase or decrease these rates. Particles deposited in non-ciliated airways have large surface-to-volume ratios, and clearance by dissolution can occur for materials generally considered insoluble. They may also be cleared as free particles either by passive transport along surface liquids or, after phagocytosis, by transport within alveolar macrophages. If the particles penetrate the epithelium, either bare or within macrophages, they may be sequestered within cells or enter the lymphatic circulation and be carried to pleural, hilar, and more distant lymph nodes. Non-toxic insoluble particles are cleared from

  9. Admixture Analysis of Spontaneous Hepatitis C Virus Clearance in Individuals of African-Descent

    PubMed Central

    Wojcik, Genevieve L.; Thio, Chloe L.; Kao, WH Linda; Latanich, Rachel; Goedert, James J.; Mehta, Shruti H.; Kirk, Gregory D.; Peters, Marion G.; Cox, Andrea L.; Kim, Arthur Y.; Chung, Raymond T.; Thomas, David L.; Duggal, Priya

    2015-01-01

    Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75–85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African-descent have lower rates of clearance compared to individuals of European-descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792,721 SNPs from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18×10−8) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations. PMID:24622687

  10. Mechanisms of failed apoptotic cell clearance by phagocyte subsets in cardiovascular disease

    PubMed Central

    2013-01-01

    Recent evidence in humans indicate that defective phagocytic clearance of dying cells is linked to progression of advanced atherosclerotic lesions, the precursor to atherothrombosis, ischemic heart disease, and leading cause of death in the industrialized world. During atherogenesis, apoptotic cell turnover in the vascular wall is counterbalanced by neighboring phagocytes with high clearance efficiency, thereby limiting cellularity and maintaining lesion integrity. However, as lesions mature, phagocytic removal of apoptotic cells (efferocytosis) becomes defective, leading to secondary necrosis, expansion of plaque necrotic cores, and susceptibility to rupture. Recent genetic causation studies in experimental rodents have implicated key molecular regulators of efferocytosis in atherosclerotic progression. These include MER tyrosine kinase (MERTK), milk fat globule-EGF factor 8 (MFGE8), and complement C1q. At the cellular level, atheromata are infiltrated by a heterogenous population of professional phagocytes, comprised of monocytes, differentiated macrophages, and CD11c+ dendritic-like cells. Each cell type is characterized by disparate clearance efficiencies and varying activities of key phagocytic signaling molecules. It is in this context that we outline a working model whereby plaque necrosis and destabilization is jointly promoted by (1) direct inhibition of core phagocytic signaling pathways and (2) expansion of phagocyte subsets with poor clearance capacity. Towards identifying targets for promoting efficient apoptotic cell clearance and resolving inflammation in atherosclerosis and during ischemic heart disease and post myocardial infarction, this review will discuss potential in vivo suppressors of efferocytosis at each stage of clearance and how these putative interventional targets may differentially affect uptake at the level of vascular phagocyte subsets. PMID:20552278

  11. Turbomachinery Clearance Control

    NASA Technical Reports Server (NTRS)

    Chupp, Raymond E.; Hendricks, Robert C.; Lattime, Scott B.; Steinetz, Bruce M.; Aksit, Mahmut F.

    2007-01-01

    Controlling interface clearances is the most cost effective method of enhancing turbomachinery performance. Seals control turbomachinery leakages, coolant flows and contribute to overall system rotordynamic stability. In many instances, sealing interfaces and coatings are sacrificial, like lubricants, giving up their integrity for the benefit of the component. They are subjected to abrasion, erosion, oxidation, incursive rubs, foreign object damage (FOD) and deposits as well as extremes in thermal, mechanical, aerodynamic and impact loadings. Tribological pairing of materials control how well and how long these interfaces will be effective in controlling flow. A variety of seal types and materials are required to satisfy turbomachinery sealing demands. These seals must be properly designed to maintain the interface clearances. In some cases, this will mean machining adjacent surfaces, yet in many other applications, coatings are employed for optimum performance. Many seals are coating composites fabricated on superstructures or substrates that are coated with sacrificial materials which can be refurbished either in situ or by removal, stripping, recoating and replacing until substrate life is exceeded. For blade and knife tip sealing an important class of materials known as abradables permit blade or knife rubbing without significant damage or wear to the rotating element while maintaining an effective sealing interface. Most such tip interfaces are passive, yet some, as for the high-pressure turbine (HPT) case or shroud, are actively controlled. This work presents an overview of turbomachinery sealing. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues.

  12. Nano-Advantage in Enhanced Drug Delivery with Biodegradable Nanoparticles: Contribution of Reduced Clearance

    PubMed Central

    Kadam, Rajendra S.; Bourne, David W. A.

    2012-01-01

    The aim of this study was to investigate the contribution of reduced apparent clearance to the enhanced exposure reported for biodegradable nanoparticles after extravascular and intravascular routes of administration. Plasma concentration profiles for drug and nanoparticle formulations after administration by intravenous, intraduodenal, and oral routes were extracted from the literature. Data were fit to pharmacokinetic models using BOOMER. The compartmental pharmacokinetic analysis of literature data for six drugs (camptothecin, 9-nitrocamptothecin, epirubicin, vinpocetine, clozapine, and cyclosporine) showed that the encapsulation of drug molecules in nanoparticles significantly reduced the apparent clearance and prolonged the apparent circulation half-life compared with those for the plain drug. Positively charged nanoparticles assessed in this study had lower apparent clearance, lower elimination rate constant values, and longer apparent circulation half-life than neutral and negatively charged nanoparticles. After oral administration, a reduction in apparent clearance contributed substantially to elevations in plasma drug exposure with nanoparticles. For the drugs and delivery systems examined, the nano-advantage in drug delivery enhancement can be explained, in part, by reduced clearance. PMID:22498894

  13. Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.

    PubMed

    Ma, Ruishuang; Xie, Rui; Yu, Chengyuan; Si, Yu; Wu, Xiaoming; Zhao, Lu; Yao, Zhipeng; Fang, Shaohong; Chen, He; Novakovic, Valerie; Gao, Chunyan; Kou, Junjie; Bi, Yayan; Thatte, Hemant S; Yu, Bo; Yang, Shufen; Zhou, Jin; Shi, Jialan

    2017-07-10

    The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

  14. Strategies to improve plasma half life time of peptide and protein drugs.

    PubMed

    Werle, M; Bernkop-Schnürch, A

    2006-06-01

    Due to the obvious advantages of long-acting peptide and protein drugs, strategies to prolong plasma half life time of such compounds are highly on demand. Short plasma half life times are commonly due to fast renal clearance as well as to enzymatic degradation occurring during systemic circulation. Modifications of the peptide/protein can lead to prolonged plasma half life times. By shortening the overall amino acid amount of somatostatin and replacing L: -analogue amino acids with D: -amino acids, plasma half life time of the derivate octreotide was 1.5 hours in comparison to only few minutes of somatostatin. A PEG(2,40 K) conjugate of INF-alpha-2b exhibited a 330-fold prolonged plasma half life time compared to the native protein. It was the aim of this review to provide an overview of possible strategies to prolong plasma half life time such as modification of N- and C-terminus or PEGylation as well as methods to evaluate the effectiveness of drug modifications. Furthermore, fundamental data about most important proteolytic enzymes of human blood, liver and kidney as well as their cleavage specificity and inhibitors for them are provided in order to predict enzymatic cleavage of peptide and protein drugs during systemic circulation.

  15. Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition.

    PubMed

    Athukuri, Bhargavi Latha; Neerati, Prasad

    2016-12-01

    Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity in vivo have been very rare. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. In the present study, the effects of gallic acid and ellagic acid pretreatment on intestinal transport and oral bioavailability of metoprolol were investigated. The intestinal transport of metoprolol was assessed by conducting an in situ single pass intestinal perfusion (SPIP) study. The bioavailability study was conducted to evaluate the pharmacokinetic parameters of orally administered metoprolol in rats. After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of metoprolol was observed at the ileum part of rat intestine. A significant improvement in the peak plasma concentration (Cmax) and area under the serum concentration-time profile (AUC) and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid. Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver. Hence, adverse herbal-drug interactions may result with concomitant ingestion of gallic acid and ellagic acid supplements and drugs that are CYP2D6 substrates. The clinical assessment of these interactions should be further investigated in human volunteers.

  16. Soluble Receptor for Advanced Glycation End-Products Predicts Impaired Alveolar Fluid Clearance in Acute Respiratory Distress Syndrome.

    PubMed

    Jabaudon, Matthieu; Blondonnet, Raiko; Roszyk, Laurence; Bouvier, Damien; Audard, Jules; Clairefond, Gael; Fournier, Mathilde; Marceau, Geoffroy; Déchelotte, Pierre; Pereira, Bruno; Sapin, Vincent; Constantin, Jean-Michel

    2015-07-15

    Levels of the soluble form of the receptor for advanced glycation end-products (sRAGE) are elevated during acute respiratory distress syndrome (ARDS) and correlate with severity and prognosis. Alveolar fluid clearance (AFC) is necessary for the resolution of lung edema but is impaired in most patients with ARDS. No reliable marker of this process has been investigated to date. To verify whether sRAGE could predict AFC during ARDS. Anesthetized CD-1 mice underwent orotracheal instillation of hydrochloric acid. At specified time points, lung injury was assessed by analysis of blood gases, alveolar permeability, lung histology, AFC, and plasma/bronchoalveolar fluid measurements of proinflammatory cytokines and sRAGE. Plasma sRAGE and AFC rates were also prospectively assessed in 30 patients with ARDS. The rate of AFC was inversely correlated with sRAGE levels in the plasma and the bronchoalveolar fluid of acid-injured mice (Spearman's ρ = -0.73 and -0.69, respectively; P < 10(-3)), and plasma sRAGE correlated with AFC in patients with ARDS (Spearman's ρ = -0.59; P < 10(-3)). Similarly, sRAGE levels were significantly associated with lung injury severity, and decreased over time in mice, whereas AFC was restored and lung injury resolved. Our results indicate that sRAGE levels could be a reliable predictor of impaired AFC during ARDS, and should stimulate further studies on the pathophysiologic implications of RAGE axis in the mechanisms leading to edema resolution. Clinical trial registered with www.clinicaltrials.gov (NCT 00811629).

  17. Myocardial imaging with 123I-hexadecenoic acid.

    PubMed

    Poe, N D; Robinson, G D; Zielinski, F W; Cabeen, W R; Smith, J W; Gomes, A S

    1977-08-01

    123I-hexadecenoic acid is a terminally iodinated, 17-carbon fatty acid analog which is rapidly degraded in the myocardium. By determining regional myocardial distribution patterns and clearance rates, it may become useful as a single agent for estimating regional myocardial perfusion and for distinguished viable ischemic tissue from infarcted tissue. The high count rates obtainable with the iodine label permit acquisition of qualitative multiprojection images in only 3 min. per view, or quantifiable single projection high count images in 10 min. Ischemic defects may be observed in anginal patients without subjecting them to stress.

  18. Novel Bioluminescent Quantitative Detection of Nucleic Acid Amplification in Real-Time

    PubMed Central

    Gandelman, Olga A.; Church, Vicki L.; Moore, Cathy A.; Kiddle, Guy; Carne, Christopher A.; Parmar, Surendra; Jalal, Hamid; Tisi, Laurence C.; Murray, James A. H.

    2010-01-01

    Background The real-time monitoring of polynucleotide amplification is at the core of most molecular assays. This conventionally relies on fluorescent detection of the amplicon produced, requiring complex and costly hardware, often restricting it to specialised laboratories. Principal Findings Here we report the first real-time, closed-tube luminescent reporter system for nucleic acid amplification technologies (NAATs) enabling the progress of amplification to be continuously monitored using simple light measuring equipment. The Bioluminescent Assay in Real-Time (BART) continuously reports through bioluminescent output the exponential increase of inorganic pyrophosphate (PPi) produced during the isothermal amplification of a specific nucleic acid target. BART relies on the coupled conversion of inorganic pyrophosphate (PPi) produced stoichiometrically during nucleic acid synthesis to ATP by the enzyme ATP sulfurylase, and can therefore be coupled to a wide range of isothermal NAATs. During nucleic acid amplification, enzymatic conversion of PPi released during DNA synthesis into ATP is continuously monitored through the bioluminescence generated by thermostable firefly luciferase. The assay shows a unique kinetic signature for nucleic acid amplifications with a readily identifiable light output peak, whose timing is proportional to the concentration of original target nucleic acid. This allows qualitative and quantitative analysis of specific targets, and readily differentiates between negative and positive samples. Since quantitation in BART is based on determination of time-to-peak rather than absolute intensity of light emission, complex or highly sensitive light detectors are not required. Conclusions The combined chemistries of the BART reporter and amplification require only a constant temperature maintained by a heating block and are shown to be robust in the analysis of clinical samples. Since monitoring the BART reaction requires only a simple light

  19. High-Clearance Six-Wheel Suspension

    NASA Technical Reports Server (NTRS)

    Bickler, Donald B.

    1992-01-01

    Multilevered suspension system gives body of vehicle high clearance and allows wheels to be steered independently. Suspension linkages above wheels enable body to skim over obstacles as high as wheel. Levers and independently steered wheels enable vehicle to climb steps 1 1/2 wheel diameters high and cross gaps 1 3/4 wide. Adaptable to off-the-road recreational vehicles, military scout vehicles, and robotic emergency vehicles.

  20. Low ground clearance vehicle detection and warning.

    DOT National Transportation Integrated Search

    2015-06-01

    A Low Ground Clearance Vehicle Detection : System (LGCVDS) determines if a commercial : motor vehicle can successfully clear a highwayrail : grade crossing and notifies the driver when : his or her vehicle cannot safely traverse the : crossing. That ...