Field test comparison of two dermal tolerance assessment methods of hand hygiene products.

PubMed

Girard, R; Carré, E; Pires-Cronenberger, S; Bertin-Mandy, M; Favier-Bulit, M C; Coyault, C; Coudrais, S; Billard, M; Regard, A; Kerhoas, A; Valdeyron, M L; Cracco, B; Misslin, P

2008-06-01

This study aimed to compare the sensitivity and workload requirement of two dermal tolerance assessment methods of hand hygiene products, in order to select a suitable pilot testing method for field tests. An observer-rating method and a self-assessment method were compared in 12 voluntary hospital departments (autumn/winter of 2005-2006). Three test-periods of three weeks were separated by two-week intervals during which the routine products were reintroduced. The observer rating method scored dryness and irritation on four-point scales. In the self-assessment method, the user rated appearance, intactness, moisture content, and sensation on a visual analogue scale which was converted into a 10-point numerical scale. Eleven products (soaps) were tested (223/250 complete reports for observer rating, 131/251 for self-assessment). Two products were significantly less well tolerated than the routine product according to the observers, four products according to the self-assessments. There was no significant difference between the two methods when products were classified according to tolerance (Fisher's test: P=0.491). For the symptom common to both assessment methods (dryness), there is a good correlation between the two methods (Spearman's Rho: P=0.032). The workload was higher for observer rating method (288 h of observer time plus 122 h of prevention team and pharmacist time compared with 15 h of prevention team and pharmacist time for self-assessment). In conclusion, the self-assessment method was considered more suitable for pilot testing, although further time should be allocated for educational measures as the return rate of complete self-assessment forms was poor.

Induced tolerance to nebulized colistin after severe reaction to the drug.

PubMed

Domínguez-Ortega, J; Manteiga, E; Abad-Schilling, C; Juretzcke, M A; Sánchez-Rubio, J; Kindelan, C

2007-01-01

Daily nebulized colistin therapy has been used as maintenance therapy for patients with chronic Pseudomonas aeruginosa infection and in treatment protocols aimed at eradicating early P aeruginosa infection. Colistin-induced nephrotoxicity and mild neurotoxic effects have been described but hypersensitivity reactions are rare. However, bronchial constriction has been reported associated with the inhalation of the antibiotic. We report the case of a 63-year-old man who had been diagnosed with bronchiectasis and bronchopleural fistula and who developed severe bronchospasm when using nebulized colistin. A skin prick test (80 mg/mL) with colistin was performed and was negative. An intradermal test was not performed due to its possible irritant effect. As our patient suffered from a tobramycin-resistant P aeruginosa infection, we started a procedure to induce tolerance to 80 mg colistin (8 mg, 16 mg, 24 mg, 32 mg, 40 mg, 80 mg) nebulized in 30-minutes-intervals. No changes in forced expiratory volume in 1 second values were observed and the patient continues on treatment twice daily after the tolerance induction with no new episodes of bronchospasm. We report the first successful procedure to induce tolerance to colistin after escalating doses of inhaled colistin.

Buffered coscheduling for parallel programming and enhanced fault tolerance

DOEpatents

Petrini, Fabrizio [Los Alamos, NM; Feng, Wu-chun [Los Alamos, NM

2006-01-31

A computer implemented method schedules processor jobs on a network of parallel machine processors or distributed system processors. Control information communications generated by each process performed by each processor during a defined time interval is accumulated in buffers, where adjacent time intervals are separated by strobe intervals for a global exchange of control information. A global exchange of the control information communications at the end of each defined time interval is performed during an intervening strobe interval so that each processor is informed by all of the other processors of the number of incoming jobs to be received by each processor in a subsequent time interval. The buffered coscheduling method of this invention also enhances the fault tolerance of a network of parallel machine processors or distributed system processors

Funnel plot control limits to identify poorly performing healthcare providers when there is uncertainty in the value of the benchmark.

PubMed

Manktelow, Bradley N; Seaton, Sarah E; Evans, T Alun

2016-12-01

There is an increasing use of statistical methods, such as funnel plots, to identify poorly performing healthcare providers. Funnel plots comprise the construction of control limits around a benchmark and providers with outcomes falling outside the limits are investigated as potential outliers. The benchmark is usually estimated from observed data but uncertainty in this estimate is usually ignored when constructing control limits. In this paper, the use of funnel plots in the presence of uncertainty in the value of the benchmark is reviewed for outcomes from a Binomial distribution. Two methods to derive the control limits are shown: (i) prediction intervals; (ii) tolerance intervals Tolerance intervals formally include the uncertainty in the value of the benchmark while prediction intervals do not. The probability properties of 95% control limits derived using each method were investigated through hypothesised scenarios. Neither prediction intervals nor tolerance intervals produce funnel plot control limits that satisfy the nominal probability characteristics when there is uncertainty in the value of the benchmark. This is not necessarily to say that funnel plots have no role to play in healthcare, but that without the development of intervals satisfying the nominal probability characteristics they must be interpreted with care. © The Author(s) 2014.

Immune tolerance to drugs. I. Long-term tolerability of rokitamycin in patients with antibiotics hypersensitivity.

PubMed

Nettis, E; Colanardi, M C; Di Paola, R; Mangialardi, G; Ferrannini, A; Tursi, A

2003-08-01

Macrolides are considered one of the safest anti-infective groups in clinical use and are well-tolerated as alternative antibiotics in patients with a previous adverse reaction to other classes of antibiotics. However there is scarce information in the literature about their long-term tolerability. The present study was performed to determine whether the results of a challenge test with rokitamycin could predict the response to ingestion of rokitamycin during illness. The study was carried out on 335 patients, who experienced adverse reactions to one or more antibiotics. All patients received peroral challenges with rokitamycin (granules or capsules). On the first day patients received a number of placebo doses equivalent to the rokitamycin doses. One week later, the test was administered by increasing doses of rokitamycin at 60 min intervals until the common daily therapeutic dose of 406.25mg was reached (31.25-93.75-125-156.25mg). A questionnaire was distributed to all subjects. In particular, subjects were asked to clarify any reactive symptom they had developed after ingestion of the drug. It was found that only 3.1% (4/129) of subjects, who used this drug, reported adverse reactions: three experienced urticaria/angioedema and one patient experienced erythema multiforme during treatment. This study, points out a low percentage of adverse reactions to rokitamycin after a negative challenge test, thus, emphasizing both safety and good predictive value as a challenge test.

Identification of atrial fibrillation using electrocardiographic RR-interval difference

NASA Astrophysics Data System (ADS)

Eliana, M.; Nuryani, N.

2017-11-01

Automated detection of atrial fibrillation (AF) is an interesting topic. It is an account of very dangerous, not only as a trigger of embolic stroke, but it’s also related to some else chronical disease. In this study, we analyse the presence of AF by determining irregularities of RR-interval. We utilize the interval comparison to measure the degree of irregularities of RR-interval in a defined segment. The series of RR-interval is segmented with the length of 10 of them. In this study, we use interval comparison for the method. We were comparing all of the intervals there each other. Then we put the threshold to define the low difference and high difference (δ). A segment is defined as AF or Normal Sinus by the number of high δ, so we put the tolerance (β) of high δ there. We have used this method to test the 23 patients data from MIT-BIH. Using the approach and the clinical data we find accuracy, sensitivity, and specificity of 84.98%, 91.99%, and 77.85% respectively.

Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism.

PubMed

Domínguez Jiménez, José Luis; Fernández Suárez, Antonio; Muñoz Colmenero, Aurora Úrsula; Fatela Cantillo, Daniel; López Pelayo, Iratxe

2017-04-01

There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (κ > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: κ, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Design and rationale of the HITTS randomized controlled trial: Effect of High-intensity Interval Training in de novo Heart Transplant Recipients in Scandinavia.

PubMed

Nytrøen, Kari; Yardley, Marianne; Rolid, Katrine; Bjørkelund, Elisabeth; Karason, Kristjan; Wigh, Julia Philip; Dall, Christian Have; Arora, Satish; Aakhus, Svend; Lunde, Ketil; Solberg, Ole Geir; Gustafsson, Finn; Prescott, Eva Irene Bossano; Gullestad, Lars

2016-02-01

There is no consensus on how, when, and at what intensity exercise should be performed and organized after heart transplantation (HTx). Most rehabilitation programs are conducted in HTx centers, which might be impractical and costly. We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in maintenance HTx recipients, but there are no studies among de novo patients, and whether HIT is feasible and superior to moderate training in HTx recipients is unclear. A total of 120 clinically stable HTx recipients older than 18 years will be recruited from 3 Scandinavian HTx centers. Participants are randomized to HIT or moderate training, shortly after surgery. All exercises are supervised in the patients' local communities. Testing at baseline and follow-up includes the following: VO2peak (primary end point), muscle strength, body composition, quality of life, myocardial performance, endothelial function, biomarkers, and progression of cardiac allograft vasculopathy. A subgroup (n = 90) will also be tested at 3-year follow-up to assess long-term effects of exercise. So far, the HIT intervention is well tolerated, without any serious adverse events. We aim to test whether decentralized HIT is feasible, safe, and superior to moderate training, and whether it will lead to significant improvement in exercise capacity and less long-term complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Orthostatic intolerance and motion sickness after parabolic flight

NASA Technical Reports Server (NTRS)

Schlegel, T. T.; Brown, T. E.; Wood, S. J.; Benavides, E. W.; Bondar, R. L.; Stein, F.; Moradshahi, P.; Harm, D. L.; Fritsch-Yelle, J. M.; Low, P. A.

2001-01-01

Because it is not clear that the induction of orthostatic intolerance in returning astronauts always requires prolonged exposure to microgravity, we investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy subjects before and after the brief micro- and hypergravity of parabolic flight. Concomitantly, we investigated the effect of parabolic flight-induced vomiting on orthostatic tolerance, R-wave-R-wave interval and arterial pressure power spectra, and carotid-cardiac baroreflex and Valsalva responses. After parabolic flight 1) 8 of 16 subjects could not tolerate 30 min of upright tilt (compared to 2 of 16 before flight); 2) 6 of 16 subjects vomited; 3) new intolerance to upright tilt was associated with exaggerated falls in total peripheral resistance, whereas vomiting was associated with increased R-wave-R-wave interval variability and carotid-cardiac baroreflex responsiveness; and 4) the proximate mode of new orthostatic failure differed in subjects who did and did not vomit, with vomiters experiencing comparatively isolated upright hypocapnia and cerebral vasoconstriction and nonvomiters experiencing signs and symptoms reminiscent of the clinical postural tachycardia syndrome. Results suggest, first, that syndromes of orthostatic intolerance resembling those developing after space flight can develop after a brief (i.e., 2-h) parabolic flight and, second, that recent vomiting can influence the results of tests of autonomic cardiovascular function commonly utilized in returning astronauts.

Personalized metabolomics for predicting glucose tolerance changes in sedentary women after high-intensity interval training.

PubMed

Kuehnbaum, Naomi L; Gillen, Jenna B; Gibala, Martin J; Britz-McKibbin, Philip

2014-08-28

High-intensity interval training (HIIT) offers a practical approach for enhancing cardiorespiratory fitness, however its role in improving glucose regulation among sedentary yet normoglycemic women remains unclear. Herein, multi-segment injection capillary electrophoresis-mass spectrometry is used as a high-throughput platform in metabolomics to assess dynamic responses of overweight/obese women (BMI > 25, n = 11) to standardized oral glucose tolerance tests (OGTTs) performed before and after a 6-week HIIT intervention. Various statistical methods were used to classify plasma metabolic signatures associated with post-prandial glucose and/or training status when using a repeated measures/cross-over study design. Branched-chain/aromatic amino acids and other intermediates of urea cycle and carnitine metabolism decreased over time in plasma after oral glucose loading. Adaptive exercise-induced changes to plasma thiol redox and orthinine status were measured for trained subjects while at rest in a fasting state. A multi-linear regression model was developed to predict changes in glucose tolerance based on a panel of plasma metabolites measured for naïve subjects in their untrained state. Since treatment outcomes to physical activity are variable between-subjects, prognostic markers offer a novel approach to screen for potential negative responders while designing lifestyle modifications that maximize the salutary benefits of exercise for diabetes prevention on an individual level.

Pharmacokinetics and tolerability of oral dosage forms of huperzine a in healthy Chinese male volunteers: a randomized, single dose, three-period, six-sequence crossover study.

PubMed

Wu, San-Lan; Gan, Jun; Rao, Jing; He, Si-Jie; Zhu, Wen-Wen; Zhao, Ying; Lv, Yong-Ning; Huang, Jian-Geng; Liu, Ya-Ni

2017-10-01

Huperzine A is a potent, reversible, and blood-brain barrier permeable acetylcholinesterase inhibitor. The aim of this study was to compare the pharmacokinetics, tolerability, and bioavailability of two formulations with the established reference formulation of huperzine A in a fasting, healthy Chinese male population. This was a randomized, single-dose, 3-period, 6-sequence crossover study. The plasma concentrations of huperzine A were determined by liquid chromatography tandem mass spectrometry. Tolerability was assessed based on subject interview, vital sign monitoring, physical examination, and routine blood and urine tests. The mean (SD) pharmacokinetic parameters of the reference drug were C max , 1.550 (0.528) ng/mL; t 1/2 , 12.092 (1.898) h; AUC 0-72h , 17.550 (3.794) ng·h/mL. Those of the test formulation A and test formulation B were C max , 1.412 (0.467), 1.521 (0.608) ng/mL; t 1/2 , 12.073 (2.068), 12.271 (1.678) h; AUC 0-72h , 15.286 (3.434) ng·h/mL, 15.673 (3.586) ng·h/mL. The 90% confidence intervals for the AUC 0-72h and C max were between 0.80 and 1.25. No adverse events were reported by the subjects or found with results of clinical laboratory test. The test and reference products met the regulatory criteria for bioequivalence in these fasting, healthy Chinese male volunteers. All three formulations appeared to be well tolerated.

Effect of Sustained Human Centrifugation on Autonomic Cardiovascular and Vestibular Function

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Benavides, Edgar W.; Harm, Deborah L.; Rupert, A. H.

2002-01-01

Repeated exposure to +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, both sustained exposure to +Gx and changes in otolith function resulting from the gravitational changes of space flight and parabolic flight may adversely affect autonomic cardiovascular function and orthostatic tolerance. HYPOTHESES: Baroreflex function and orthostatic tolerance are acutely improved by a single sustained (30 min) exposure to +3Gz but not +3Gx. Moreover, after 30 min of +3Gx, any changes that occur in autonomic cardiovascular function will relate commensurately to changes in otolith function. METHODS: Twenty-two healthy human subjects were first exposed to 5 min of +3 Gz centrifugation and then subsequently up to a total of30 min of either +3Gz (n = 15) or +3Gx (n = 7) centrifugation. Tests of autonomic cardiovascular function both before and after both types of centrifugation included: (a) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; (b) carotid-cardiac baroreflex tests; ( c) Valsalva tests; and (d) 30-min head-up tilt (HUT) tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: All four +3Gz subjects who were intolerant to HUT before centrifugation became tolerant to HUT after centrifugation. The operational point of the carotid-cardiac baroreflex and the Valsalva-related baroreflex were also enhanced in the +3Gz group but not in the +3Gx group. No significant vestibular-autonomic relationships were detected, other than a significant vestibular-cerebrovascular interaction reported previously. CONCLUSIONS: A single, sustained exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance whereas a similar exposure to +3 Gx centrifugation appears to have less effect.

Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial.

PubMed

Puccio, Giuseppe; Alliet, Philippe; Cajozzo, Cinzia; Janssens, Elke; Corsello, Giovanni; Sprenger, Norbert; Wernimont, Susan; Egli, Delphine; Gosoniu, Laura; Steenhout, Philippe

2017-04-01

The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). Infant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.

Tolerance to Effects of Cocaine on Behavior under a Response-Initiated Fixed-Interval Schedule

ERIC Educational Resources Information Center

Weaver, Matthew T.; Branch, Marc N.

2008-01-01

Tolerance to effects of cocaine can be modulated by schedules of reinforcement. With multiple ratio schedules, research has shown an inverse relationship between ratio requirement and amount of tolerance that resulted from daily administration of the drug. In contrast, tolerance to the effects of cocaine on behavior under multiple interval…

Evaluation of Analgesia, Tolerance, and the Mechanism of Action of Morphine-6-O-Sulfate Across Multiple Pain Modalities in Sprague-Dawley Rats.

PubMed

Yadlapalli, Jai Shankar K; Dogra, Navdeep; Walbaum, Anqi W; Wessinger, William D; Prather, Paul L; Crooks, Peter A; Dobretsov, Maxim

2017-09-01

Morphine-6-O-sulfate (M6S) is a mixed μ/δ-opioid receptor (OR) agonist and potential alternative to morphine for treatment of chronic multimodal pain. To provide more support for this hypothesis, the antinociceptive effects of M6S and morphine were compared in tests that access a range of pain modalities, including hot plate threshold (HPT), pinprick sensitivity threshold (PST) and paw pressure threshold tests. Acutely, M6S was 2- to 3-fold more potent than morphine in HPT and PST tests, specifically, derived from best-fit analysis of dose-response relationships of morphine/M6S half-effective dose (ED50) ratios (lower, upper 95% confidence interval [CI]) were 2.8 (2.0-5.8) in HPT and 2.2 (2.1, 2.4) in PST tests. No differences in analgesic drug potencies were detected in the PPT test (morphine/M6S ED50 ratio 1.2 (95% CI, 0.8-1.4). After 7 to 9 days of chronic treatment, tolerance developed to the antinociceptive effects of morphine, but not to M6S, in all 3 pain tests. Morphine-tolerant rats were not crosstolerant to M6S. The antinociceptive effects of M6S were not sensitive to κ-OR antagonists. However, the δ-OR antagonist, naltrindole, blocked M6S-induced antinociception by 55% ± 4% (95% CI, 39-75) in the HPT test, 94% ± 4% (95% CI, 84-105) in the PST test, and 5% ± 17% (95% CI, -47 to 59) or 51% ± 14% (95% CI, 14-84; 6 rats per each group) in the paw pressure threshold test when examined acutely or after 7 days of chronic treatment, respectively. Activity via δ-ORs thus appears to be an important determinant of M6S action. M6S also exhibited favorable antinociceptive and tolerance profiles compared with morphine in 3 different antinociceptive assays, indicating that M6S may serve as a useful alternative for rotation in morphine-tolerant subjects.

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

PubMed

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

2018-02-01

Numerous studies have shown that mild-to-moderate intensity or resistance exercise training improves physical capacities such as, peak oxygen consumption, maximal tolerated power and strength in multiple sclerosis patients. However, few studies have evaluated the effects of high-intensity interval training (HIIT) associated to with resistance training. Only few studies have analyzed difference between men and women before and after combined training. Moreover, the evaluation of exercise between ambulatory multiple sclerosis patients without disability (Expanded Disability Status Score [EDSS] 0-3) and patients with disabilities (EDSS 3.5-5) was not largely published. The main objective of our study was to determine if HIIT combined with resistance training improved aerobic and strength capacities as well as quality of life in multiple sclerosis patients and if gender and disabilities play a role in these changes. This study was an open-label uncontrolled study. The study was performed outside from conventional care facilities and including homebased training. Twenty-six multiple sclerosis patients have completed the program (19 women, 7 men; mean age 44.6±7.9 years, EDSS 2 [0-5]). We conducted a 12-week program of high-intensity interval training combined with resistance training at body weight. Peak oxygen consumption, maximal tolerated power, lactates, isokinetic strength of quadriceps and hamstrings (at 90°/s, 180°/s, and 240°/s) and quality of life were evaluated before and after the program. Peak oxygen consumption and maximum tolerated power improved by 13.5% and 9.4%, respectively. Isokinetic muscle strength increased in both quadriceps and hamstrings at each speed, with a rebalancing of strength between the two legs in quadriceps. Quality of life was also enhanced in three domains. Women showed better improvements than men in V̇O2peak, maximal tolerated power, lactates at the end of test, and heart rate peak, strength in both quadriceps and hamstrings mostly at low speed, and quality of life. The two EDSS groups increased V̇O2peak and strength. Our study has shown that HIIT combined with resistance exercise training induced an improvement in physical capacity and quality of life. Moreover, this study allowed patients, irrespective of their sex or EDSS score, to resume exercise autonomously. The results of the study showed that aerobic training at moderate intensity is not the single type of training tolerated by multiple sclerosis patients. High-intensity interval training is well tolerated too and can be used in clinical rehabilitation with resistance training, in both men and women with and without disabilities.

Effect of 30-min +3 Gz centrifugation on vestibular and autonomic cardiovascular function

NASA Technical Reports Server (NTRS)

Schlegel, Todd T.; Wood, Scott J.; Brown, Troy E.; Harm, Deborah L.; Rupert, A. H.

2003-01-01

INTRODUCTION: Repeated exposure to increased +Gz enhances human baroreflex responsiveness and improves tolerance to cardiovascular stress. However, it is not known whether such enhancements might also result from a single, more prolonged exposure to increased +Gz. Our study was designed to investigate whether baroreflex function and orthostatic tolerance are acutely improved by a single prolonged exposure to +3 Gz, and moreover, whether changes in autonomic cardiovascular function resulting from exposure to increased +Gz are correlated with changes in otolith function. METHODS: We exposed 15 healthy human subjects to +3 Gz centrifugation for up to 30 min or until symptoms of incipient G-induced loss of consciousness (G-LOC) ensued. Tests of autonomic cardiovascular function both before and after centrifugation included: 1) power spectral determinations of beat-to-beat R-R intervals and arterial pressures; 2) carotid-cardiac baroreflex tests; 3) Valsalva tests; and 4) 30-min head-up tilt tests. Otolith function was assessed during centrifugation by the linear vestibulo-ocular reflex and both before and after centrifugation by measurements of ocular counter-rolling and dynamic posturography. RESULTS: Of the 15 subjects who underwent prolonged +3 Gz, 4 were intolerant to 30 min of head-up tilt before centrifugation but became tolerant to such tilt after centrifugation. The Valsalva-related baroreflex as well as a measure of the carotid-cardiac baroreflex were also enhanced after centrifugation. No significant vestibular-autonomic relationships were detected beyond a vestibular-cerebrovascular interaction reported earlier in a subset of seven participants. CONCLUSIONS: A single prolonged exposure to +3 Gz centrifugation acutely improves baroreflex function and orthostatic tolerance.

High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

PubMed

Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

2015-08-15

The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state. Copyright © 2015 the American Physiological Society.

Atropine unmasks bed-rest effect - A spectral analysis of cardiac interbeat intervals

NASA Technical Reports Server (NTRS)

Goldberger, Ary L.; Goldwater, Danielle; Bhargava, Valmik

1986-01-01

Heart rate spectral data obtained for 10 male subjects between 35-49 years following orthostatic tolerance testing with lower body negative pressure prebed rest and after 7-10 days of bed rest, while on placebo and after intravenous atropine are analyzed. Comparison of the spectral atropine rms for subjects prebed rest and after bed rest reveal a decrease from 63 + or - 24 ms to 40 + or - 23 ms. It is observed that heart rate interval variability for subjects after bed rest and with atropine is reduced; the heart rate at bed rest with atropine is increased from 70.4 + or - 12.4 beats/min prebed rest to 83.7 + or - 18.9 beats/min; and the exercise tolerance time for subjects in the atropine prebed-rest phase (658 + or - 352 s) is higher than the bed-rest phase (505 + or - 252 s). It is noted that bed rest impairs the cardiovascular capacity to adaptively modulate physiological responses, atropine exposes bed-rest deconditioning effects, and spectral analysis is useful for studying the effects of bed-rest deconditioning on cardiac dynamics.

A study of ventricular contractility and other parameters possibly related to vasodepressor syncope

NASA Technical Reports Server (NTRS)

Hyatt, K. H.; Sullivan, R. W.; Spears, W. R.; Vetter, W. R.

1973-01-01

The effects of diminished orthostatic and exercise tolerance resulting from prolonged bedrest were studied by noninvasion methods to determine if alterations in myocardial contractility were induced by bedrest. These methods were apexcardiography, systolic time intervals, and echocardiography. It is concluded that bedrest causes detrimental alterations in the contractile state of the myocardium which accounts for the decreases in maximal oxygen uptaken during exercise after bedrest. Tabulated test data are included.

Peptide Glutamine Supplementation for Tolerance of Intermittent Exercise in Soccer Players

PubMed Central

Favano, Alessandra; Santos-Silva, Paulo Roberto; Nakano, Eduardo Yoshio; Pedrinelli, André; Hernandez, Arnaldo José; Greve, Julia Maria D’Andrea

2008-01-01

OBJECTIVE To investigate whether supplementation of carbohydrate together with peptide glutamine would increase exercise tolerance in soccer players. METHODS Nine male soccer players (mean age: 18.4 ± 1.1 years; body mass: 69.2 ± 4.6 kg; height: 175.5 ± 7.3 cm; and maximum oxygen consumption of 57.7 ± 4.8 ml·kg−1·min−1) were evaluated. All of them underwent a cardiopulmonary exercise test and followed a protocol that simulated the movements of a soccer game in order to evaluate their tolerance to intermittent exercise. By means of a draw, either carbohydrate with peptide glutamine (CARBOGLUT: 50g of maltodextrin + 3.5g of peptide glutamine in 250 ml of water) or carbohydrate alone (CARBO: 50g of maltodextrin in 250 ml of water) was administered in order to investigate the enhancement of the soccer players’ performances. The solution was given thirty minutes before beginning the test, which was performed twice with a one-week interval between tests. RESULTS A great improvement in the time and distance covered was observed when the athletes consumed the CARBOGLUT mixture. Total distance covered was 12750 ± 4037m when using CARBO, and 15571 ± 4184m when using CARBOGLUT (p<0.01); total duration of tolerance was 73 ± 23 min when using CARBO and 88 ± 24 min when using CARBOGLUT (p<0.01). CONCLUSION The CARBOGLUT mixture was more efficient in increasing the distance covered and the length of time for which intermittent exercise was tolerated. CARBOGLUT also reduced feelings of fatigue in the players compared with the use of the CARBO mixture alone. PMID:18297203

Personalized Metabolomics for Predicting Glucose Tolerance Changes in Sedentary Women After High-Intensity Interval Training

PubMed Central

Kuehnbaum, Naomi L.; Gillen, Jenna B.; Gibala, Martin J.; Britz-McKibbin, Philip

2014-01-01

High-intensity interval training (HIIT) offers a practical approach for enhancing cardiorespiratory fitness, however its role in improving glucose regulation among sedentary yet normoglycemic women remains unclear. Herein, multi-segment injection capillary electrophoresis-mass spectrometry is used as a high-throughput platform in metabolomics to assess dynamic responses of overweight/obese women (BMI > 25, n = 11) to standardized oral glucose tolerance tests (OGTTs) performed before and after a 6-week HIIT intervention. Various statistical methods were used to classify plasma metabolic signatures associated with post-prandial glucose and/or training status when using a repeated measures/cross-over study design. Branched-chain/aromatic amino acids and other intermediates of urea cycle and carnitine metabolism decreased over time in plasma after oral glucose loading. Adaptive exercise-induced changes to plasma thiol redox and orthinine status were measured for trained subjects while at rest in a fasting state. A multi-linear regression model was developed to predict changes in glucose tolerance based on a panel of plasma metabolites measured for naïve subjects in their untrained state. Since treatment outcomes to physical activity are variable between-subjects, prognostic markers offer a novel approach to screen for potential negative responders while designing lifestyle modifications that maximize the salutary benefits of exercise for diabetes prevention on an individual level. PMID:25164777

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

PubMed

Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

2016-07-01

New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms

NASA Technical Reports Server (NTRS)

Cowings, P. S.; Toscano, W. B.

2000-01-01

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.

Autogenic-feedback training exercise is superior to promethazine for control of motion sickness symptoms.

PubMed

Cowings, P S; Toscano, W B

2000-10-01

Motion sickness symptoms affect approximately 50% of the crew during space travel and are commonly treated with intramuscular injections of promethazine. The purpose of this paper is to compare the effectiveness of three treatments for motion sickness: intramuscular injections (i.m.) of promethazine, a physiological training method (autogenic-feedback training exercise [AFTE]), and a no-treatment control. An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair. For the present paper, motion sickness tolerance, symptom reports, and physiological responses of these subjects were compared to matched subjects selected from an existing database who received either AFTE or no treatment. Three groups of 11 men, between the ages of 33 and 40 years, were matched on the number of rotations tolerated during their initial rotating-chair motion sickness test. The motion sickness test procedures and the 7-day interval between tests were the same for all subjects. The drug group was tested under four treatment conditions: baseline (no injections), a 25 mg dose of promethazine, a 50 mg dose of promethazine, and a placebo of sterile saline. AFTE subjects were given four 30-minute AFTE sessions before their second, third, and fourth motion sickness tests (6 hours total). The no-treatment control subjects were only given the four rotating-chair tests. Motion sickness tolerance was significantly increased after 4 hours of AFTE when compared to either 25 mg (p < 0.00003) or 50 mg (p < 0.00001) of promethazine. The control and promethazine groups did not differ. AFTE subjects reported fewer or no symptoms at higher rotational velocities than subjects in the control or promethazine groups. The primary physiological effect of promethazine was an inhibition of skin conductance level. The AFTE group showed significantly less heart rate and skin conductance variability during motion sickness tests administered after training.

Effects of 4-aminopyridine on cardiac repolarization, PR interval, and heart rate in patients with spinal cord injury.

PubMed

Isoda, Wakana C; Segal, Jack L

2003-02-01

To determine the effects of 4-aminopyridine (4-AP) on heart rate and PR, QT, and QTc intervals in patients with longstanding spinal cord injury (SCI). Randomized, active-treatment-controlled, dose level-blinded study, with allocation concealed. University-affiliated, tertiary care medical center. Sixty otherwise healthy male and female outpatients with traumatic SCI of more than 1 year's duration. Intervention. Oral administration and dose titration to tolerance of an immediate-release formulation of 4-AP. The PR interval, heart rate, QT interval, and QTc interval obtained from standard 12-lead electrocardiograms (ECGs) at baseline (before administration of 4-AP) and after 1 month of treatment were compared. The QTc intervals were derived by using Bazett's formula (equation) incorporated into standard computerized analyses of 12-lead ECG printouts. The paired t test was performed to test for the significance of differences between means and variances. No statistically significant differences were noted in heart rate or between ECG time intervals measured at baseline and after 1 month of treatment with 4-AP among all patients with SCI or between subgroups stratified by injury level (tetraplegia, paraplegia) or sex. During the 1-month period that 4-AP was administered, the heart rate and PR, QT, and QTc intervals all remained unchanged and stayed well within normal range in comparison to literature-derived control values. 4-Aminopyridine does not appear to influence the length of cardiac time intervals or heart rate and, hence, is unlikely to cause potentially life-threatening ventricular dysrrhythmias when administered long-term and taken orally in dosages of up to 30 mg/day. Specifically, cardiac repolarization (QTc interval) is unaffected in patients with SCI who continuously receive 4-AP for up to 1 month.

How to regress and predict in a Bland-Altman plot? Review and contribution based on tolerance intervals and correlated-errors-in-variables models.

PubMed

Francq, Bernard G; Govaerts, Bernadette

2016-06-30

Two main methodologies for assessing equivalence in method-comparison studies are presented separately in the literature. The first one is the well-known and widely applied Bland-Altman approach with its agreement intervals, where two methods are considered interchangeable if their differences are not clinically significant. The second approach is based on errors-in-variables regression in a classical (X,Y) plot and focuses on confidence intervals, whereby two methods are considered equivalent when providing similar measures notwithstanding the random measurement errors. This paper reconciles these two methodologies and shows their similarities and differences using both real data and simulations. A new consistent correlated-errors-in-variables regression is introduced as the errors are shown to be correlated in the Bland-Altman plot. Indeed, the coverage probabilities collapse and the biases soar when this correlation is ignored. Novel tolerance intervals are compared with agreement intervals with or without replicated data, and novel predictive intervals are introduced to predict a single measure in an (X,Y) plot or in a Bland-Atman plot with excellent coverage probabilities. We conclude that the (correlated)-errors-in-variables regressions should not be avoided in method comparison studies, although the Bland-Altman approach is usually applied to avert their complexity. We argue that tolerance or predictive intervals are better alternatives than agreement intervals, and we provide guidelines for practitioners regarding method comparison studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Quantitative sensory testing and pain tolerance in patients with mild to moderate Alzheimer disease compared to healthy control subjects.

PubMed

Jensen-Dahm, Christina; Werner, Mads U; Dahl, Jørgen B; Jensen, Troels Staehelin; Ballegaard, Martin; Hejl, Anne-Mette; Waldemar, Gunhild

2014-08-01

Patients with Alzheimer disease (AD) report pain less frequently than their cognitively intact peers. It has been hypothesized that pain processing is altered in AD. The aim of this study was to investigate agreement and reliability of 3 pain sensitivity tests and to examine pain threshold and tolerance in patients with AD. We examined 29 patients with mild to moderate AD and 29 age- and gender-matched healthy control subjects with quantitative sensory testing, ie, assessments of detection threshold (warmth detection threshold [WDT]) and pain threshold (heat pain threshold [HPT], pressure algometry, cold pressor test), and assessments of tolerance (pressure algometry, cold pressor test). All procedures were done twice on day 1, 1 hour apart, and repeated on day 2. We found no difference between groups for WDT (patient vs control subjects: mean [95% confidence interval]: 35.5°C [33.4°C to 37.6°C] vs 35.4°C [34.3°C to 36.5°C], P=.8) or HPT (41.2°C [40.0°C to 42.4°C] vs 42.3°C [41.1°C to 43.5°C], P=.24). We observed comparable thresholds for pressure algometry (median [25% to 75% interquartile range]: 120 kPa [100 to 142 kPa] vs 131 kPa [113 to 192 kPa], P=.10), but significantly lower tolerance in AD patients (213 kPa [188 to 306 kPa] vs 289 kPa [262 to 360 kPa], P=.008). No differences were found for the cold pressor test. The study demonstrated good replicability of the sensory testing data with comparable data variability, for both groups, which supports the use of these methods in studies of patients with mild to moderate AD. Contrary to previous studies, we observed a reduced pain tolerance in patients with mild to moderate AD, which suggests that the reduced report of pain cannot be explained by reduced processing of painful stimuli. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Picrotoxin-induced behavioral tolerance and altered susceptibility to seizures: effects of naloxone.

PubMed

Thomas, J; Nores, W L; Pariser, R

1993-07-01

The role of opiate mechanisms in the development of tolerance and altered susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with naloxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then tested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencies to different types of seizures, the duration of postseizure immobility, and the number of focal seizure episodes were scored. In the vehicle-treated group, repeated picrotoxin injections led to an increased susceptibility to myoclonic and focal seizures and to decreased duration of postseizure immobility. Naloxone pretreatment significantly decreased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related behaviors. Naloxone did not alter the development of tolerance or sensitivity, indicating that naloxone-insensitive opiate mechanisms or nonopiate mechanisms may be involved in these processes.

A Framework for Probabilistic Evaluation of Interval Management Tolerance in the Terminal Radar Control Area

NASA Technical Reports Server (NTRS)

Hercencia-Zapana, Heber; Herencia-Zapana, Heber; Hagen, George E.; Neogi, Natasha

2012-01-01

Projections of future traffic in the national airspace show that most of the hub airports and their attendant airspace will need to undergo significant redevelopment and redesign in order to accommodate any significant increase in traffic volume. Even though closely spaced parallel approaches increase throughput into a given airport, controller workload in oversubscribed metroplexes is further taxed by these approaches that require stringent monitoring in a saturated environment. The interval management (IM) concept in the TRACON area is designed to shift some of the operational burden from the control tower to the flight deck, placing the flight crew in charge of implementing the required speed changes to maintain a relative spacing interval. The interval management tolerance is a measure of the allowable deviation from the desired spacing interval for the IM aircraft (and its target aircraft). For this complex task, Formal Methods can help to ensure better design and system implementation. In this paper, we propose a probabilistic framework to quantify the uncertainty and performance associated with the major components of the IM tolerance. The analytical basis for this framework may be used to formalize both correctness and probabilistic system safety claims in a modular fashion at the algorithmic level in a way compatible with several Formal Methods tools.

Efficacy, Safety, and Tolerability of Armodafinil Therapy for Hypersomnia Associated With Dementia With Lewy Bodies: A Pilot Study

PubMed Central

Lapid, Maria I.; Kuntz, Karen M.; Mason, Sara S.; Aakre, Jeremiah A.; Lundt, Emily S.; Kremers, Walter; Allen, Laura A.; Drubach, Daniel A.; Boeve, Bradley F.

2017-01-01

Background/Aims Hypersomnia is common in dementia with Lewy bodies (DLB). We assessed the efficacy, safety, and tolerability of armodafinil for hypersomnia associated with DLB. Methods We performed a 12-week pilot trial of armodafinil therapy (125–250 mg orally daily) in DLB outpatients with hypersomnia. Patients underwent neurologic examinations, neuropsychological battery, laboratory testing, electrocardiography, and polysomnography. Efficacy was assessed at 2, 4, 8, and 12 weeks. Safety assessment included laboratory examinations, QTc interval, and heart rate. Tolerability was assessed by analysis of adverse events. Data were analyzed using the last-observation-carried-forward method. Results Of 20 participants, 17 completed the protocol. Median age was 72 years, most were men (80%), and most had spouses as caregivers. Epworth Sleepiness Scale (P<.001), Maintenance of Wakefulness Test (P=.003), and Clinical Global Impression of Change (P<.001) scores improved at week 12. Neuropsychiatric Inventory total score (P=.003), visual hallucinations (P=.003), and agitation (P=.02) improved at week 4. Caregiver overall quality of life improved at week 12 (P=.004). No adverse events occurred. Conclusion These pilot data suggest improvements in hypersomnia and wakefulness and reasonable safety and tolerability of armodafinil therapy in hypersomnolent patients with DLB. Our findings inform the use of pharmacologic strategies to manage hypersomnolence in these patients. PMID:28448998

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

PubMed

Tripathy, Devjit; Cobb, Jeff E; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Reaven, Peter D; Musi, Nicolas; Ferrannini, Ele; DeFronzo, Ralph A

2015-05-01

The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min(-1)·kgwbm(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M(Q) correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin in predicting incident diabetes. In IGT subjects, Quantose M(Q) parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M(Q) may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.

A Novel Insulin Resistance Index to Monitor Changes in Insulin Sensitivity and Glucose Tolerance: the ACT NOW Study

PubMed Central

Tripathy, Devjit; Cobb, Jeff E.; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C.; Banerji, MaryAnn; Bray, George A.; Buchanan, Thomas A.; Clement, Stephen C.; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Reaven, Peter D.; Musi, Nicolas; Ferrannini, Ele

2015-01-01

Objective: The objective was to test the clinical utility of Quantose MQ to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose MQ is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Research Design and Methods: Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Results: Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13–0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose MQ increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min−1·kgwbm−1) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose MQ correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose MQ outperformed both Matsuda and fasting insulin in predicting incident diabetes. Conclusions: In IGT subjects, Quantose MQ parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose MQ may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients. PMID:25603459

Some consideration for evaluation of structural integrity of aging aircraft

NASA Astrophysics Data System (ADS)

Terada, Hiroyuki; Asada, Hiroo

The objective of this paper is to examine the achievement and the limitation of state-of-the-art of the methodology of damage tolerant design and the subjects to be solved for further improvement. The topics discussed are: the basic concept of full-scale fatigue testing, fracture mechanics applications, repair of detected damages, inspection technology, and determination of inspection intervals, reliability assessment for practical application, and the importance of various kinds of data acquisition.

Assessing the performance of handheld glucose testing for critical care.

PubMed

Kost, Gerald J; Tran, Nam K; Louie, Richard F; Gentile, Nicole L; Abad, Victor J

2008-12-01

We assessed the performance of a point-of-care (POC) glucose meter system (GMS) with multitasking test strip by using the locally-smoothed (LS) median absolute difference (MAD) curve method in conjunction with a modified Bland-Altman difference plot and superimposed International Organization for Standardization (ISO) 15197 tolerance bands. We analyzed performance for tight glycemic control (TGC). A modified glucose oxidase enzyme with a multilayer-gold, multielectrode, four-well test strip (StatStriptrade mark, NOVA Biomedical, Waltham, MA) was used. There was no test strip calibration code. Pragmatic comparison was done of GMS results versus paired plasma glucose measurements from chemistry analyzers in clinical laboratories. Venous samples (n = 1,703) were analyzed at 35 hospitals that used 20 types of chemistry analyzers. Erroneous results were identified using the Bland-Altman plot and ISO 15197 criteria. Discrepant values were analyzed for the TGC interval of 80-110 mg/dL. The GMS met ISO 15197 guidelines; 98.6% (410 of 416) of observations were within tolerance for glucose <75 mg/dL, and for > or =75 mg/dL, 100% were within tolerance. Paired differences (handheld minus reference) averaged -2.2 (SD 9.8) mg/dL; the median was -1 (range, -96 to 45) mg/dL. LS MAD curve analysis revealed satisfactory performance below 186 mg/dL; above 186 mg/dL, the recommended error tolerance limit (5 mg/dL) was not met. No discrepant values appeared. All points fell in Clarke Error Grid zone A. Linear regression showed y = 1.018x - 0.716 mg/dL, and r2 = 0.995. LS MAD curves draw on human ability to discriminate performance visually. LS MAD curve and ISO 15197 performance were acceptable for TGC. POC and reference glucose calibration should be harmonized and standardized.

C-reactive protein and cold-pressor tolerance in the general population: the Tromsø Study.

PubMed

Schistad, Elina Iordanova; Stubhaug, Audun; Furberg, Anne-Sofie; Engdahl, Bo Lars; Nielsen, Christopher Sivert

2017-07-01

The aim of this study was to examine whether increases in severity of subclinical inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), increased experimental pain sensitivity, measured by cold-pressor tolerance, and to test whether this relationship is independent of chronic pain. A large population-based study from 2007 to 2008, the sixth Tromsø Study, provided data from 12,981 participants. For the present analysis, complete data for 10,274 participants (age: median 58 years) were available. The main outcome measure was cold-pressor tolerance, tested by placing the dominant hand in circulating cold water (3°C) for a maximum of 106 seconds. Cox proportional hazard models, treating hand withdrawal during the cold-pressor test as the event and enduring the full test time as censored data, were used to investigate the relationship between hs-CRP levels (≤3 or >3 mg/L) and cold-pressure tolerance. The fully adjusted model was controlled for age, sex, education, body mass index, smoking status, alcohol consumption, emotional distress, statin usage, and self-reported presence of chronic pain. Additional analysis was performed in participants without chronic pain. Higher levels of hs-CRP were negatively related to cold-pressor tolerance (hazard ratio [HR] = 1.24, 95% confidence interval [CI], 1.12-1.37, P < 0.001), adjusted for age and sex. This relationship remained essentially unaltered after controlling for potential confounders (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001), as well as for the presence of chronic pain (HR = 1.22, 95% CI, 1.09-1.36, P < 0.001). The present data show that subclinical inflammation is related to increased pain sensitivity, suggesting a potential role of inflammation in experimental pain which may be of importance for the development of clinical pain.

The effect on glycaemic control of low-volume high-intensity interval training versus endurance training in individuals with type 2 diabetes.

PubMed

Winding, Kamilla M; Munch, Gregers W; Iepsen, Ulrik W; Van Hall, Gerrit; Pedersen, Bente K; Mortensen, Stefan P

2018-05-01

To evaluate whether high-intensity interval training (HIIT) with a lower time commitment can be as effective as endurance training (END) on glycaemic control, physical fitness and body composition in individuals with type 2 diabetes. A total of 29 individuals with type 2 diabetes were allocated to control (CON; no training), END or HIIT groups. Training groups received 3 training sessions per week consisting of either 40 minutes of cycling at 50% of peak workload (END) or 10 1-minute intervals at 95% of peak workload interspersed with 1 minute of active recovery (HIIT). Glycaemic control (HbA1c, oral glucose tolerance test, 3-hour mixed meal tolerance test with double tracer technique and continuous glucose monitoring [CGM]), lipolysis, VO 2 peak and body composition were evaluated before and after 11 weeks of intervention. Exercise training increased VO 2 peak more in the HIIT group (20% ± 20%) compared with the END group (8% ± 9%) despite lower total energy expenditure and time usage during the training sessions. HIIT decreased whole body and android fat mass compared with the CON group. In addition, visceral fat mass, HbA1c, fasting glucose, postprandial glucose, glycaemic variability and HOMA-IR decreased after HIIT. The reduced postprandial glucose in the HIIT group was driven primarily by a lower rate of exogenous glucose appearance. In the CON group, postprandial lipolysis was augmented over the 11-week control period. Despite a ~45% lower training volume, HIIT resulted in similar or even better improvements in physical fitness, body composition and glycemic control compared to END. HIIT therefore appears to be an important time-efficient treatment for individuals with type 2 diabetes. © 2017 John Wiley & Sons Ltd.

Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study.

PubMed

Johansson, Magdalena; Lind, Marcus; Jansson, Jan-Håkan; Fhärm, Eva; Johansson, Lars

2018-05-01

It remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Västerbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. An objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83-1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97-1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91-1.00). There were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE. Copyright © 2018 Elsevier Ltd. All rights reserved.

Conformity and statistical tolerancing

NASA Astrophysics Data System (ADS)

Leblond, Laurent; Pillet, Maurice

2018-02-01

Statistical tolerancing was first proposed by Shewhart (Economic Control of Quality of Manufactured Product, (1931) reprinted 1980 by ASQC), in spite of this long history, its use remains moderate. One of the probable reasons for this low utilization is undoubtedly the difficulty for designers to anticipate the risks of this approach. The arithmetic tolerance (worst case) allows a simple interpretation: conformity is defined by the presence of the characteristic in an interval. Statistical tolerancing is more complex in its definition. An interval is not sufficient to define the conformance. To justify the statistical tolerancing formula used by designers, a tolerance interval should be interpreted as the interval where most of the parts produced should probably be located. This tolerance is justified by considering a conformity criterion of the parts guaranteeing low offsets on the latter characteristics. Unlike traditional arithmetic tolerancing, statistical tolerancing requires a sustained exchange of information between design and manufacture to be used safely. This paper proposes a formal definition of the conformity, which we apply successively to the quadratic and arithmetic tolerancing. We introduce a concept of concavity, which helps us to demonstrate the link between tolerancing approach and conformity. We use this concept to demonstrate the various acceptable propositions of statistical tolerancing (in the space decentring, dispersion).

Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial

PubMed Central

Puccio, Giuseppe; Alliet, Philippe; Cajozzo, Cinzia; Janssens, Elke; Corsello, Giovanni; Sprenger, Norbert; Wernimont, Susan; Egli, Delphine; Gosoniu, Laura; Steenhout, Philippe

2017-01-01

ABSTRACT Objectives: The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. Methods: Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk–based infant formula (control, n = 87) or the same formula with 1.0 g/L 2′fucosyllactose (2′FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. Results: Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: −0.30 [−1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [−3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004–0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). Conclusions: Infant formula with 2′FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies. PMID:28107288

Whey protein isolate improves acid and bile tolerances of Streptococcus thermophilus ST-M5 and Lactobacillus delbrueckii ssp. bulgaricus LB-12.

PubMed

Vargas, Luis A; Olson, Douglas W; Aryana, Kayanush J

2015-04-01

Acid tolerance and bile tolerance are important probiotic characteristics. Whey proteins contain branched-chain amino acids, which play a role in muscle building and are popular among athletes. Increasing emphasis is being placed on diets containing less carbohydrate, less fat, and more protein. The effect of incremental additions of whey protein isolate (WPI) on probiotic characteristics of pure cultures is not known. The objective of this study was to determine the influence of added WPI on acid tolerance and bile tolerance of pure cultures of Streptococcus thermophilus ST-M5 and Lactobacillus bulgaricus LB-12. The WPI was used at 0 (control), 1, 2 and 3% (wt/vol). Assessment of acid tolerance was conducted on pure cultures at 30-min intervals for 2h of acid exposure and bile tolerance at 1-h intervals for 5h of bile exposure. Use of 1, 2, and 3% WPI improved acid tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12. The highest counts for acid tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12 were obtained when 3% WPI was used. Use of 2 and 3% WPI improved bile tolerance of Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12 over 5h of bile exposure. The use of WPI is recommended to improve acid and bile tolerance of the yogurt culture bacteria Strep. thermophilus ST-M5 and Lb. bulgaricus LB-12. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Increased prevalence of abnormal glucose tolerance among obese siblings of children with type 2 diabetes.

PubMed

Magge, Sheela N; Stettler, Nicolas; Jawad, Abbas F; Levitt Katz, Lorraine E

2009-04-01

To test the hypothesis that overweight siblings of children with type 2 diabetes mellitus (T2DM) have a higher prevalence of abnormal glucose tolerance (AGT) compared with other overweight children. This was a cross-sectional study of overweight (body mass index [BMI] >or= 95(th) percentile) subjects, age 8 to 17 years, with at least 1 sibling age >or= 12 years. The primary outcome was AGT, as assessed by the oral glucose tolerance test (2-hour glucose >or= 140 mg/dL). The secondary outcome was insulin resistance by homeostasis model assessment (HOMA). The sibling (n=20) and control (n=42) groups were similar in terms of age, sex, racial distribution (largely African American), pubertal status, and BMI. The prevalence of AGT in the sibling group was 40.0% (n=8), compared with 14.3% (n=6) in controls (P= .048, Fisher exact test; unadjusted odds ratio=4.0; 95% confidence interval=1.2 to 13.5). Univariate analysis did not identify confounders for either outcome. There were no significant differences in HOMA or hemoglobin A1c between the 2 groups. Overweight siblings of children with T2DM had 4 times greater odds of having AGT compared with other overweight children. This group may represent a particularly high-risk population to target for screening and pediatric T2DM prevention.

Effects of Cocaine on Performance under Fixed-Interval Schedules with a Small Tandem Ratio Requirement

ERIC Educational Resources Information Center

Pinkston, Jonathan W.; Branch, Marc N.

2004-01-01

Daily administration of cocaine often results in the development of tolerance to its effects on responding maintained by fixed-ratio schedules. Such effects have been observed to be greater when the ratio value is small, whereas less or no tolerance has been observed at large ratio values. Similar schedule-parameter-dependent tolerance, however,…

Benefits of interval-training on fatigue and functional capacities in Charcot-Marie-Tooth disease.

PubMed

El Mhandi, Lhassan; Millet, Guillaume Y; Calmels, Paul; Richard, Antoine; Oullion, Roger; Gautheron, Vincent; Féasson, Léonard

2008-05-01

Exercise intolerance and undue fatigue are common complaints in patients with Charcot-Marie-Tooth (CMT) disease. Reduced physical ability is due directly to the disease, but it is also due to physical deconditioning. The aim of this study was to test whether 24 weeks of interval-training exercise (ITE) cycling can significantly improve physiological, neuromuscular, and functional capacities and alleviate fatigue in CMT patients. Eight CMT patients (4 CMT1A and 4 CMT2) participated in ITE for 3 nonconsecutive days per week. Cardiovascular fitness, muscle strength, fatigue resistance, and functional capacities were measured before and after 12 weeks of supervised hospital training and again after another 12 weeks of unsupervised home training. Training was well tolerated. There were significant improvements in cardiorespiratory capacities, isokinetic concentric strength, and functional ability measurements. All patients experienced an improvement in their self-reported visual analogic scale for fatigue and pain during training. However, there was no significant change in their isometric force production and indices of fatigue resistance after training. Although the improvement in exercise tolerance may be due in part to reversal of the deconditioning effect of their related sedentary lifestyle, this clinical trial suggests that ITE can benefit CMT patients especially in their functional performance and subjective perception of pain and fatigue. Moreover, the improvement observed at the end of the first supervised period ITE was maintained after the second unsupervised home period, although there was no further improvement in performance and tolerance.

Combining Short-Term Interval Training with Caloric Restriction Improves ß-Cell Function in Obese Adults.

PubMed

Francois, Monique E; Gilbertson, Nicole M; Eichner, Natalie Z M; Heiston, Emily M; Fabris, Chiara; Breton, Marc; Mehaffey, J Hunter; Hassinger, Taryn; Hallowell, Peter T; Malin, Steven K

2018-06-03

Although low-calorie diets (LCD) improve glucose regulation, it is unclear if interval exercise (INT) is additive. We examined the impact of an LCD versus LCD + INT training on ß-cell function in relation to glucose tolerance in obese adults. Twenty-six adults (Age: 46 ± 12 year; BMI 38 ± 6 kg/m²) were randomized to 2-week of LCD (~1200 kcal/day) or energy-matched LCD + INT (60 min/day alternating 3 min at 90 and 50% HRpeak). A 2 h 75 g oral glucose tolerance test (OGTT) was performed. Insulin secretion rates (ISR) were determined by deconvolution modeling to assess glucose-stimulated insulin secretion ([GSIS: ISR/glucose total area under the curve (tAUC)]) and ß-cell function (Disposition Index [DI: GSIS/IR]) relative to skeletal muscle (Matsuda Index), hepatic (HOMA-IR) and adipose (Adipose-IR fasting ) insulin resistance (IR). LCD + INT, but not LCD alone, reduced glucose and total-phase ISR tAUC (Interactions: p = 0.04 and p = 0.05, respectively). Both interventions improved skeletal muscle IR by 16% ( p = 0.04) and skeletal muscle and hepatic DI (Time: p < 0.05). Improved skeletal muscle DI was associated with lower glucose tAUC ( r = -0.57, p < 0.01). Thus, LCD + INT improved glucose tolerance more than LCD in obese adults, and these findings relate to ß-cell function. These data support LCD + INT for preserving pancreatic function for type 2 diabetes prevention.

Comparative evaluation of the efficacy and tolerability of itopride hydrochloride and domperidone in patients with non-ulcer dyspepsia.

PubMed

Sawant, Prabha; Das, H S; Desai, Nutan; Kalokhe, S; Patil, S

2004-08-01

Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia (NUD). To assess the efficacy and tolerability of a new prokinetic agent, itopride hydrochloride in patients of NUD and compare it with domperidone. Fifty-six patients who fulfilled the inclusion and exclusion criteria were enrolled in the study. Patients underwent upper gastrointestinal endoscopy to rule out organic pathology as a cause for their symptoms. The patient's symptoms were graded on a 4-point scale (0 to 3) at the beginning of treatment and at the end of Week-one and Week-two Patients were randomly allocated to receive either one tablet of itopride hydrochloride 50mg three times daily or one tablet of domperidone 10mg three times daily for two weeks. Pre-treatment and post-treatment hemogram, liver function and renal function tests, prolactin level and ECG were done in all patients. The response to therapy was evaluated by assessing the relief of symptoms at the end of two weeks on a 5-point scale. Statistical analysis was done using two-tailed paired t-test; Wilcoxon matched pairs ranks sum test, Mann-Whitney-U test and chi-square test as applicable. Of the fifty-five patients enrolled in the study (age range of 18-60 yrs, median age of 35yrs), 26 were males and twenty nine were females. They had a median duration of symptoms for 4 weeks. Twenty-seven patients received itopride and 28 received domperidone. One patient did not follow up in the domperidone group, thus 54 patients were evaluable for analysis. Moderate to complete symptomatic relief was observed in 22 (81%) patients in the itopride group and 19 patients (70%) in the domperidone group (p > 0.05, NS). Both the drugs were well tolerated and neither caused prolongation of QT interval nor any abnormality in any serum biochemistry values. Therapy with itopride resulted in good symptomatic relief, was safe, well tolerated and comparable in efficacy to domperidone in relieving the symptoms of NUD. By virtue of its efficacy and tolerability, it could be an ideal choice for providing symptomatic relief to patients suffering from non-ulcer dyspepsia.

Adaptive Test Schemes for Control of Paratuberculosis in Dairy Cows.

PubMed

Kirkeby, Carsten; Græsbøll, Kaare; Nielsen, Søren Saxmose; Christiansen, Lasse Engbo; Toft, Nils; Halasa, Tariq

2016-01-01

Paratuberculosis is a chronic infection that in dairy cattle causes reduced milk yield, weight loss, and ultimately fatal diarrhea. Subclinical animals can excrete bacteria (Mycobacterium avium ssp. paratuberculosis, MAP) in feces and infect other animals. Farmers identify the infectious animals through a variety of test-strategies, but are challenged by the lack of perfect tests. Frequent testing increases the sensitivity but the costs of testing are a cause of concern for farmers. Here, we used a herd simulation model using milk ELISA tests to evaluate the epidemiological and economic consequences of continuously adapting the sampling interval in response to the estimated true prevalence in the herd. The key results were that the true prevalence was greatly affected by the hygiene level and to some extent by the test-frequency. Furthermore, the choice of prevalence that will be tolerated in a control scenario had a major impact on the true prevalence in the normal hygiene setting, but less so when the hygiene was poor. The net revenue is not greatly affected by the test-strategy, because of the general variation in net revenues between farms. An exception to this is the low hygiene herd, where frequent testing results in lower revenue. When we look at the probability of eradication, then it is correlated with the testing frequency and the target prevalence during the control phase. The probability of eradication is low in the low hygiene herd, and a test-and-cull strategy should probably not be the primary strategy in this herd. Based on this study we suggest that, in order to control MAP, the standard Danish dairy farm should use an adaptive strategy where a short sampling interval of three months is used when the estimated true prevalence is above 1%, and otherwise use a long sampling interval of one year.

Role of age and injury mechanism on cervical spine injury tolerance from head contact loading.

PubMed

Yoganandan, Narayan; Chirvi, Sajal; Voo, Liming; Pintar, Frank A; Banerjee, Anjishnu

2018-02-17

The objective of this study was to determine the influence of age and injury mechanism on cervical spine tolerance to injury from head contact loading using survival analysis. This study analyzed data from previously conducted experiments using post mortem human subjects (PMHS). Group A tests used the upright intact head-cervical column experimental model. The inferior end of the specimen was fixed, the head was balanced by a mechanical system, and natural lordosis was removed. Specimens were placed on a testing device via a load cell. The piston applied loading at the vertex region. Spinal injuries were identified using medical images. Group B tests used the inverted head-cervical column experimental model. In one study, head-T1 specimens were fixed distally, and C7-T1 joints were oriented anteriorly, preserving lordosis. Torso mass of 16 kg was added to the specimen. In another inverted head-cervical column study, occiput-T2 columns were obtained, an artificial head was attached, T1-T2 was fixed, C4-C5 disc was maintained horizontal in the lordosis posture, and C7-T1 was unconstrained. The specimens were attached to the drop test carriage carrying a torso mass of 15 kg. A load cell at the inferior end measured neck loads in both studies. Axial neck force and age were used as the primary response variable and covariate to derive injury probability curves using survival analysis. Group A tests showed that age is a significant (P < .05) and negative covariate; that is, increasing age resulted in decreasing force for the same risk. Injuries were mainly vertebral body fractures and concentrated at one level, mid-to-lower cervical spine, and were attributed to compression-related mechanisms. However, age was not a significant covariate for the combined data from group B tests. Both group B tests produced many soft tissue injuries, at all levels, from C1 to T1. The injury mechanism was attributed to mainly extension. Multiple and noncontiguous injuries occurred. Injury probability curves, ±95% confidence intervals, and normalized confidence interval sizes representing the quality of the mean curve are given for different data sets. For compression-related injuries, specimen age should be used as a covariate or individual specimen data may be prescaled to derive risk curves. For distraction- or extension-related injuries, however, specimen age need not be used as a covariate in the statistical analysis. The findings from these tests and survival analysis indicate that the age factor modulates human cervical spine tolerance to impact injury.

Persistent post-surgical pain and experimental pain sensitivity in the Tromsø study: comorbid pain matters.

PubMed

Johansen, Aslak; Schirmer, Henrik; Stubhaug, Audun; Nielsen, Christopher S

2014-02-01

In a large survey incorporating medical examination (N=12,981), information on chronic pain and surgery was collected, and sensitivity to different pain modalities was tested. Tolerance to the cold pressor test was analysed with survival statistics for 10,486 individuals, perceived cold pressor pain intensity was calculated for 10,367 individuals, heat pain threshold was assessed for 4,054 individuals, and pressure pain sensitivity for 4,689 individuals. Persistent post-surgical pain, defined by self-report, was associated with lower cold pressor tolerance (sex-adjusted hazard ratio=1.34, 95% confidence interval=1.08-1.66), but not when adjusting for other chronic pain. Other experimental pain modalities did not differentiate between individuals with or without post-surgical pain. Of the individuals with chronic pain (N=3352), 6.2% indicated surgery as a cause, although only 0.5% indicated surgery as the only cause. The associations found between persistent post-surgical pain and cold pressor tolerance is largely explained by the co-existence of chronic pain from other causes. We conclude that most cases of persistent post-surgical pain are coexistent with other chronic pain, and that, in an unselected post-surgical population, persistent post-surgical pain is not significantly associated with pain sensitivity when controlling for comorbid pain from other causes. A low prevalence of self-reported persistent pain from surgery attenuates statistically significant associations. We hypothesize that general chronic pain is associated with central changes in pain processing as expressed by reduced tolerance for the cold pressor test. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Dose dense cyclophosphamide, methotrexate, fluorouracil is feasible at 14-day intervals: a pilot study of every-14-day dosing as adjuvant therapy for breast cancer.

PubMed

Drullinsky, Pamela; Sugarman, Steven M; Fornier, Monica N; D'Andrea, Gabriella; Gilewski, Teresa; Lake, Diana; Traina, Tiffany; Wasserheit-Lieblich, Carolyn; Sklarin, Nancy; Atieh-Graham, Deena; Mills, Nancy; Troso-Sandoval, Tiffany; Seidman, Andrew D; Yuan, Jeffrey; Patel, Hamangi; Patil, Sujata; Norton, Larry; Hudis, Clifford

2010-12-01

Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule. Thirty-eight patients with early-stage breast cancer were accrued from March 2008 through June 2008. They were treated every 14 days with C 600, M 40, F 600 (all mg/m2) with PEG-filgrastim (Neulasta®) support on day 2 of each cycle. The primary endpoint was tolerability using a Simon's 2-stage optimal design. The design would effectively discriminate between true tolerability (as protocol-defined) rates of ≤ 60% and ≥ 80%. The median age was 52-years-old (range, 38-78 years of age). Twenty-nine of the 38 patients completed 8 cycles of CMF at 14-day intervals. Dose-dense adjuvant CMF is tolerable and feasible at 14-day intervals with PEG-filgrastim support.

Statistical methods for estimating normal blood chemistry ranges and variance in rainbow trout (Salmo gairdneri), Shasta Strain

USGS Publications Warehouse

Wedemeyer, Gary A.; Nelson, Nancy C.

1975-01-01

Gaussian and nonparametric (percentile estimate and tolerance interval) statistical methods were used to estimate normal ranges for blood chemistry (bicarbonate, bilirubin, calcium, hematocrit, hemoglobin, magnesium, mean cell hemoglobin concentration, osmolality, inorganic phosphorus, and pH for juvenile rainbow (Salmo gairdneri, Shasta strain) trout held under defined environmental conditions. The percentile estimate and Gaussian methods gave similar normal ranges, whereas the tolerance interval method gave consistently wider ranges for all blood variables except hemoglobin. If the underlying frequency distribution is unknown, the percentile estimate procedure would be the method of choice.

Cardiac reserve during weightlessness simulation and shuttle flight

NASA Technical Reports Server (NTRS)

Goldberger, A. L.

1985-01-01

Bedrest deconditioning is suspected to reduce cardiac function. However, quantitation of subtle decreases in cardiac reserve may be difficult. Normal subjects show considerable variability in heart rate response, reflected by a relatively broadband interbeat interval power spectrum. We hypothesized that the deconditioning effects of bedrest would induce narrowing of this spectrum, reflecting a reduction in the autonomically-modulated variability in heart rate. Ten aerobically conditioned men (average 35-50 years) underwent orthostatic tolerance testing with lower body negative pressure pre-bedrest and after 10 days of bedrest, while on placebo and after intravenous atropine. Spectra were derived by Fourier analysis of 128 interbeat interval data sets from subjects with sufficient numbers of beats during matched periods of the protocol. Data suggest that atropine unmasks the deconditioning effect of bedrest in athletic men, evidenced by a reduction in interbeat interval spectral power compared with placebo. Spectral analysis offers a new means of quantitating the effects of bedrest deconditioning and autonomic perturbations on cardiac dynamics.

Glucose tolerance test - non-pregnant

MedlinePlus

Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test; Diabetic - glucose tolerance test ... The most common glucose tolerance test is the oral glucose ... the test begins, a sample of blood will be taken. You will then ...

Impact of exercise on diurnal and nocturnal markers of glycaemic variability and oxidative stress in obese individuals with type 2 diabetes or impaired glucose tolerance.

PubMed

Farabi, Sarah S; Carley, David W; Smith, Donald; Quinn, Lauretta

2015-09-01

We measured the effects of a single bout of exercise on diurnal and nocturnal oxidative stress and glycaemic variability in obese subjects with type 2 diabetes mellitus or impaired glucose tolerance versus obese healthy controls. Subjects (in random order) performed either a single 30-min bout of moderate-intensity exercise or remained sedentary for 30 min at two separate visits. To quantify glycaemic variability, standard deviation of glucose (measured by continuous glucose monitoring system) and continuous overlapping net glycaemic action of 1-h intervals (CONGA-1) were calculated for three 12-h intervals during each visit. Oxidative stress was measured by 15-isoprostane F(2t) levels in urine collections for matching 12-h intervals. Exercise reduced daytime glycaemic variability (ΔCONGA-1 = -12.62 ± 5.31 mg/dL, p = 0.04) and urinary isoprostanes (ΔCONGA-1 = -0.26 ± 0.12 ng/mg, p = 0.04) in the type 2 diabetes mellitus/impaired glucose tolerance group. Daytime exercise-induced change in urinary 15-isoprostane F(2t) was significantly correlated with both daytime standard deviation (r = 0.68, p = 0.03) and with subsequent overnight standard deviation (r = 0.73, p = 0.027) in the type 2 diabetes mellitus/impaired glucose tolerance group. Exercise significantly impacts the relationship between diurnal oxidative stress and nocturnal glycaemic variability in individuals with type 2 diabetes mellitus/impaired glucose tolerance. © The Author(s) 2015.

Long-term lifestyle intervention with optimized high-intensity interval training improves body composition, cardiometabolic risk, and exercise parameters in patients with abdominal obesity.

PubMed

Gremeaux, Vincent; Drigny, Joffrey; Nigam, Anil; Juneau, Martin; Guilbeault, Valérie; Latour, Elise; Gayda, Mathieu

2012-11-01

The aim of this study was to study the impact of a combined long-term lifestyle and high-intensity interval training intervention on body composition, cardiometabolic risk, and exercise tolerance in overweight and obese subjects. Sixty-two overweight and obese subjects (53.3 ± 9.7 yrs; mean body mass index, 35.8 ± 5 kg/m(2)) were retrospectively identified at their entry into a 9-mo program consisting of individualized nutritional counselling, optimized high-intensity interval exercise, and resistance training two to three times a week. Anthropometric measurements, cardiometabolic risk factors, and exercise tolerance were measured at baseline and program completion. Adherence rate was 97%, and no adverse events occurred with high-intensity interval exercise training. Exercise training was associated with a weekly energy expenditure of 1582 ± 284 kcal. Clinically and statistically significant improvements were observed for body mass (-5.3 ± 5.2 kg), body mass index (-1.9 ± 1.9 kg/m(2)), waist circumference (-5.8 ± 5.4 cm), and maximal exercise capacity (+1.26 ± 0.84 metabolic equivalents) (P < 0.0001 for all parameters). Total fat mass and trunk fat mass, lipid profile, and triglyceride/high-density lipoprotein ratio were also significantly improved (P < 0.0001). At program completion, the prevalence of metabolic syndrome was reduced by 32.5% (P < 0.05). Independent predictors of being a responder to body mass and waist circumference loss were baseline body mass index and resting metabolic rate; those for body mass index decrease were baseline waist circumference and triglyceride/high-density lipoprotein cholesterol ratio. A long-term lifestyle intervention with optimized high-intensity interval exercise improves body composition, cardiometabolic risk, and exercise tolerance in obese subjects. This intervention seems safe, efficient, and well tolerated and could improve adherence to exercise training in this population.

Hypertension Risk Subsequent to Gestational Dysglycemia Is Modified by Race/Ethnicity.

PubMed

Bentley-Lewis, Rhonda; Huynh, Jennifer; Li, Sylvia; Wenger, Julia; Thadhani, Ravi

2016-01-01

Gestational diabetes mellitus is associated with an increased risk of type 2 diabetes mellitus and hypertension. Additionally, gestational dysglycemia has been associated with an increased risk of type 2 diabetes mellitus but not yet associated with hypertension subsequent to pregnancy in long-term follow-up. Therefore, we set out to examine this relationship as well as the role of race/ethnicity in modifying this relationship. We analyzed a prospective observational cohort followed between 1998 and 2007. There were 17 655 women with self-reported race/ethnicity and full-term, live births. A 1-hour 50 g oral glucose-load test and a 3-hour 100 g oral glucose-tolerance test enabled third trimester stratification of women into 1 of 4 glucose-tolerance groups: (1) normal (n=15 056); (2) abnormal glucose-load test (n=1558); (3) abnormal glucose-load and -tolerance tests (n=520); and (4) gestational diabetes mellitus (n=521). Women were then followed for a mean±standard deviation of 4.1±2.9 years after delivery for the development of hypertension. Although gestational diabetes mellitus was associated with an increased risk of hypertension after pregnancy (odds ratio [95% confidence interval]: 1.58 [1.02, 2.45]; P=0.04), dysglycemia defined by an abnormal glucose-load test predicted hypertension only among black women (4.52 [1.24, 16.52]; P=0.02). The risk of hypertension after pregnancy among dysglycemia groups not meeting criteria for gestational diabetes mellitus varied based on the race/ethnicity of the population. Further research on the implications of the intersection of race/ethnicity and gestational dysglycemia on subsequent hypertension is warranted. © 2015 American Heart Association, Inc.

Development of Behavioral Toxicology Methodology for Interactive Exposure Regimens.

DTIC Science & Technology

1983-12-01

exposures conducted at weekly Interval had Identical effects. Five consecutive daily exposures resulted In partial tolerance to the disruptive effects...No. 2001C) for which the tap line was also located at the top of the chamber head measured the negative pressure of chamber Interior in relation to...result In partial tolerance development. lIT RESEARCH INSTITUTE 44 Although In contrast to Ator and Merigan’s finding, tolerance was not complete after

Rank score and permutation testing alternatives for regression quantile estimates

USGS Publications Warehouse

Cade, B.S.; Richards, J.D.; Mielke, P.W.

2006-01-01

Performance of quantile rank score tests used for hypothesis testing and constructing confidence intervals for linear quantile regression estimates (0 ≤ τ ≤ 1) were evaluated by simulation for models with p = 2 and 6 predictors, moderate collinearity among predictors, homogeneous and hetero-geneous errors, small to moderate samples (n = 20–300), and central to upper quantiles (0.50–0.99). Test statistics evaluated were the conventional quantile rank score T statistic distributed as χ2 random variable with q degrees of freedom (where q parameters are constrained by H 0:) and an F statistic with its sampling distribution approximated by permutation. The permutation F-test maintained better Type I errors than the T-test for homogeneous error models with smaller n and more extreme quantiles τ. An F distributional approximation of the F statistic provided some improvements in Type I errors over the T-test for models with > 2 parameters, smaller n, and more extreme quantiles but not as much improvement as the permutation approximation. Both rank score tests required weighting to maintain correct Type I errors when heterogeneity under the alternative model increased to 5 standard deviations across the domain of X. A double permutation procedure was developed to provide valid Type I errors for the permutation F-test when null models were forced through the origin. Power was similar for conditions where both T- and F-tests maintained correct Type I errors but the F-test provided some power at smaller n and extreme quantiles when the T-test had no power because of excessively conservative Type I errors. When the double permutation scheme was required for the permutation F-test to maintain valid Type I errors, power was less than for the T-test with decreasing sample size and increasing quantiles. Confidence intervals on parameters and tolerance intervals for future predictions were constructed based on test inversion for an example application relating trout densities to stream channel width:depth.

High intensity interval exercise is an effective alternative to moderate intensity exercise for improving glucose tolerance and insulin sensitivity in adolescent boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Tomlinson, Owen W; Vlachopoulos, Dimitris; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-11-01

High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys. Within-measures design with counterbalanced experimental conditions. Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale. The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES < 0.01). A single bout of time efficient HIIE is an effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Influences on Cocaine Tolerance Assessed under a Multiple Conjunctive Schedule of Reinforcement

ERIC Educational Resources Information Center

Yoon, Jin Ho; Branch, Marc N.

2009-01-01

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the…

Attenuation of Morphine-Induced Tolerance and Dependence by Pretreatment with Cerebrolysin in Male rats.

PubMed

Ghavimi, Hamed; Darvishi, Sara; Ghanbarzadeh, Saeed

2018-01-01

Dependence and tolerance to morphine are major problems which limit its chronic clinical application. This study was aimed to investigate the attenuation effect of Cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,), on the development of Morphine-induced dependence and tolerance. Male Wistar rats were selected randomly and divided into different groups (n=8) including: a control group, groups received additive doses of morphine (5-25 mg/kg, ip, at an interval of 12 h until tolerance completion), and groups pretreated with Cerebrolysin (40, 80 and 160 mg/kg, ip, before morphine administration). Development of tolerance was assessed by tail-flick test and the attenuation effect of Cerebrolysin on morphine-induced dependence was evaluated after injection of naloxone (4 mg/kg, ip, 12 h after the morning dose of morphine). Seven distinct withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, wet dog shake and teeth grinding were recorded for 45 min and total withdrawal score (TWS) was calculated. Results showed that administration of Cerebrolysin could prolonged development (10 and 14 days in administration of 80 mg/kg and 160 mg/kg Cerebrolysin) and completion (4, 10 and 14 days in administration of 40, 80 and 160 mg/kg Cerebrolysin, respectively) of tolerance. Results also indicated that administration of Cerebrolysin (40, 80 and 160 mg/kg) could significantly decreased the TWS value (62±2, 77±4 and 85±6%, respectively). In conclusion, it was found that pretreatment with Cerebrolysin could attenuated morphine-induced tolerance and dependence. © Georg Thieme Verlag KG Stuttgart · New York.

Insulin and C-peptide secretion in non-obese patients with polycystic ovarian disease.

PubMed

Mahabeer, S; Jialal, I; Norman, R J; Naidoo, C; Reddi, K; Joubert, S M

1989-09-01

Plasma glucose, immunoreactive insulin (IRI) and C-peptide responses during an oral glucose tolerance test (oGTT) were assessed in 11 non-obese patients with polycystic ovarian disease (PCOD) and 11 reference subjects matched for age, height and weight. Also, 6 patients with PCOD and 6 normal women were subjected to intravenous glucose tolerance testing (ivGTT) On oGTT, all subjects exhibited normal glucose tolerance; however, PCOD patients had significantly higher mean plasma glucose levels at 30, 60, 90 and 120 min and higher mean incremental glucose areas. In addition the patients with polycystic ovaries showed higher mean basal IRI and C-peptide levels, higher mean glucose stimulated IRI and C-peptide levels and higher mean incremental IRI and C-peptide values. The molar ratios of C-peptide/IRI were significantly lower in the PCOD group at all time intervals after glucose stimulation when compared to the normal women. During ivGTT, there were significantly higher mean glucose levels at 5, 40, 50 and 60 min in the PCOD group when compared to the reference group. The IRI response to intravenous glucose in the PCOD women was similar to the reference group. The findings on oGTT suggest that non-obese patients with PCOD have increased pancreatic IRI secretion as well as impaired hepatic extraction of the hormone.

Bioavailability of oxycodone after administration of a new prolonged-release once-daily tablet formulation in healthy subjects, in comparison to an established twice-daily tablet
.

PubMed

Scheidel, Bernhard; Maritz, Martina A; Gschwind, Yves J; Steigerwald, Kerstin; Guth, Volker; Kovacs, Peter; Rey, Helene

2017-11-01

To evaluate and to compare the bioavailability, the influence of food intake on the bioavailability, and the safety and tolerability of a newly-developed oxycodone once-daily (OOD) prolonged-release tablet with an established oxycodone twice-daily (OTD) prolonged-release tablet after single-dose administration under fasting or fed conditions as well as after multiple-dose administration. Three single-center, open-label, randomized, balanced, two-treatment, two-period, two-sequence crossover studies were conducted. In each study, 36 healthy volunteers were randomized to receive 10 mg oxycodone daily as OOD (oxycodone HCL 10-mg PR tablets XL (Develco Pharma Schweiz AG, Pratteln, Switzerland); administration of 1 tablet in the morning) or as OTD (reference formulation: oxygesic 5-mg tablets (Mundipharma GmbH, Limburg an der Lahn, Germany); administration of 1 tablet in the morning and 1 tablet in the evening). Tablets were administered once daily or twice daily under fasting conditions (study 1) or under fed conditions (study 2) as well as after multiple-dose administration (study 3). A sufficient number of blood samples were taken for describing plasma profiles and for calculation of pharmacokinetic parameters. Plasma concentrations of oxycodone were determined by LC-MS/MS. Safety and tolerability were monitored and assessed in all three studies. Plasma profiles of OOD reveal sustained concentrations of oxycodone over the complete dosing interval of 24 hours. In comparison to the OTD reference formulation, the OOD test formulation showed a slightly slower increase of concentrations within the absorption phase and similar plasma concentrations at the maximum and at the end of the dosing interval (24 hours). Extent of bioavailability (AUC), maximum plasma concentrations (C_max), and plasma concentrations at the end of the dosing interval (C_τ,ss,24h) of OOD could be classified as comparable to OTD considering 90% confidence intervals (CIs) and acceptance limits of 80.00 - 125.00%. Bioavailability of OOD was not influenced by concomitant food intake. OOD and OTD were generally well tolerated, a difference between the two products could not be observed. The new 10-mg OOD formulation provides sustained oxycodone plasma concentrations over the dosing interval of 24 hours and is suitable for once-daily administration. Bioavailability of OOD could be classified as comparable to the twice-daily administration of the OTD reference formulation. The new formulation widens and optimizes the range of strong opioid drug products in patient-centered therapy of chronic pain with simplified dosing and better compliance.
.

Nutritional equivalency evaluation of transgenic maize grain from event DP-O9814O-6 and transgenic soybeans containing event DP-356O43-5: laying hen performance and egg quality measures.

PubMed

McNaughton, J; Roberts, M; Rice, D; Smith, B; Hinds, M; Delaney, B; Iiams, C; Sauber, T

2011-02-01

The objective of this study was to compare the nutritional performance of laying hens fed maize grain from event DP-Ø9814Ø-6 (98140; gat4621 and zm-hra genes) and processed soybean meal from soybeans containing event DP-356Ø43-5 (356043; gat4601 and gm-hra genes), individually or in combination, with the performance of hens fed diets containing nontransgenic maize and soybean meal. Healthy pullets (n = 216) placed in cages (3 hens/cage) were randomly assigned to 9 dietary treatments (8 cages/treatment): nontransgenic controls 1, 2, and 3 (comparable genetic background controls for 98140, 356043, and 98140 + 356043, respectively); reference 1, reference 2, and reference 3 (commercially available nontransgenic maize-soybean meal sources); and 98140 (test 1), 356043 (test 2), and 98140 + 356043 (test 3). The experiment was divided into three 4-wk phases (24 to 28 wk, 28 to 32 wk, and 32 to 36 wk of age), during which time hens were fed mash diets. Performance (BW, feed intake, and egg production) and egg quality data were collected. Data were analyzed using a mixed model ANOVA; differences between the control and respective test group means were considered significant at P < 0.05. Data generated from the reference groups were used only in the estimation of experimental variability and in generating the tolerance interval. Body weight and BW gain, egg production, and production efficiency for hens fed the test diets were similar to the respective values for hens fed the corresponding control diets. Haugh unit measures and egg component weights were similar between the respective test and control groups, and no differences were observed in quality grades or crack measures. All observed values of the control and test groups were within the calculated tolerance intervals. This research indicates that the performance and egg quality of hens fed diets containing 98140 maize grain, 356043 soybean meal, or a combination of the 2 was comparable with that of hens fed diets formulated with nontransgenic maize grain or soybean meal control diets with comparable genetic backgrounds.

Near infrared and Raman spectroscopy as Process Analytical Technology tools for the manufacturing of silicone-based drug reservoirs.

PubMed

Mantanus, J; Rozet, E; Van Butsele, K; De Bleye, C; Ceccato, A; Evrard, B; Hubert, Ph; Ziémons, E

2011-08-05

Using near infrared (NIR) and Raman spectroscopy as PAT tools, 3 critical quality attributes of a silicone-based drug reservoir were studied. First, the Active Pharmaceutical Ingredient (API) homogeneity in the reservoir was evaluated using Raman spectroscopy (mapping): the API distribution within the industrial drug reservoirs was found to be homogeneous while API aggregates were detected in laboratory scale samples manufactured with a non optimal mixing process. Second, the crosslinking process of the reservoirs was monitored at different temperatures with NIR spectroscopy. Conformity tests and Principal Component Analysis (PCA) were performed on the collected data to find out the relation between the temperature and the time necessary to reach the crosslinking endpoints. An agreement was found between the conformity test results and the PCA results. Compared to the conformity test method, PCA had the advantage to discriminate the heating effect from the crosslinking effect occurring together during the monitored process. Therefore the 2 approaches were found to be complementary. Third, based on the HPLC reference method, a NIR model able to quantify the API in the drug reservoir was developed and thoroughly validated. Partial Least Squares (PLS) regression on the calibration set was performed to build prediction models of which the ability to quantify accurately was tested with the external validation set. The 1.2% Root Mean Squared Error of Prediction (RMSEP) of the NIR model indicated the global accuracy of the model. The accuracy profile based on tolerance intervals was used to generate a complete validation report. The 95% tolerance interval calculated on the validation results indicated that each future result will have a relative error below ±5% with a probability of at least 95%. In conclusion, 3 critical quality attributes of silicone-based drug reservoirs were quickly and efficiently evaluated by NIR and Raman spectroscopy. Copyright © 2011 Elsevier B.V. All rights reserved.

Oxcarbazepine versus carbamazepine monotherapy for partial onset seizures.

PubMed

Koch, Marcus W; Polman, Susanne Kl

2009-10-07

Partial onset seizures are often treated with the standard antiepileptic drug carbamazepine. Oxcarbazepine is a newer antiepileptic drug related to carbamazepine that is claimed to be better tolerated. To compare efficacy and tolerability of carbamazepine and oxcarbazepine monotherapy for partial onset seizures. We searched the Cochrane Epilepsy Group Specialised Register (4 August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library issue 3, 2009), MEDLINE (January 1966 to May 2008), reference lists of relevant articles and conference proceedings. We also contacted manufacturers and researchers in the field for published or unpublished data. Blinded and unblinded randomised controlled trials of carbamazepine versus oxcarbazepine monotherapy for partial onset seizures. Both authors independently assessed trial quality, according to the guidelines in the Cochrane Reviewer's Handbook, and extracted information about study population, type of intervention, outcome measures and study design. All analyses in this review are by intention-to-treat. We tested for statistical heterogeneity among the identified studies using the chi-squared test. Three trials (723 participants) were included. Only one trial used adequate outcome measures of efficacy; therefore, the results pertaining to efficacy are based on a single trial, whereas the results pertaining to adverse events are based on all three included trials. There was no overall difference in time to treatment withdrawal between the two drugs (hazard ratio (HR) of oxcarbazepine (OXC) versus carbamazepine (CBZ): 1.04, 95% confidence interval (CI) 0.78 to 1.39). Further analyses showed no significant difference in treatment withdrawal for unacceptable side effects (HR of OXC versus CBZ: 0.85, 95% CI 0.59 to 1.24) and in treatment withdrawal for inadequate seizure control (HR of OXC versus CBZ: 1.33, 95% CI 0.82 to 2.15). Oxcarbazepine and carbamazepine appeared to be similarly effective and well tolerated although the confidence intervals around estimates were wide and do not rule out the possibility of important differences existing. Significantly fewer patients on carbamazepine treatment developed nausea or vomiting, or both (odds ratio of OXC versus CBZ: 3.15, 95% CI 1.39 to 7.14). Oxcarbazepine and carbamazepine appear to be similarly effective and well tolerated. However, the possibility of important differences existing between these drugs cannot be ruled out.

Hormone and Cytokine Responses to Repeated Endotoxin Exposures-No Evidence of Endotoxin Tolerance After 5 Weeks in Humans.

PubMed

Rittig, Nikolaj; Thomsen, Henrik H; Bach, Ermina; Jørgensen, Jens Otto L; Møller, Niels

2015-07-01

Endotoxin administrations are used in experimental models of inflammatory disease. Short-term endotoxin tolerance in response to repeated endotoxin exposure is well known, but the duration of endotoxin tolerance in humans remains unknown. The main purpose of this study was to test whether endotoxin tolerance is present in vivo when separating endotoxin exposures with more than 5 weeks, a time span often used between individual investigations in clinical experimental studies. Seventeen healthy young men were exposed twice to Escherichia coli endotoxin. The inflammatory response was calculated as area under the curve between the first and second endotoxin exposures for heart rate, mean arterial blood pressure, temperature, cortisol, tumor necrosis factor α, and interleukin (IL)-1β, IL-6, and IL-10. The median interval between exposures was 90 days (range, 37-244). The ratio between the inflammatory responses during the second and the first endotoxin exposures was 0.89 ± 0.09 (P = 0.28) for tumor necrosis factor α, 0.96 ± 0.07 (P = 0.53) for IL-1β, 0.97 ± 0.11 (P = 0.78) for IL-6, 1.30 ± 0.18 (P = 0.12) for IL-10, and 0.92 ± 0.04 (P = 0.10) for cortisol. Our data do not show evidence of in vivo tolerance to repeated endotoxin exposure when administrations are separated with at least 5 weeks. This observation is important in the planning and interpretation of future experimental endotoxin studies.

L-statistics for Repeated Measurements Data With Application to Trimmed Means, Quantiles and Tolerance Intervals.

PubMed

Assaad, Houssein I; Choudhary, Pankaj K

2013-01-01

The L -statistics form an important class of estimators in nonparametric statistics. Its members include trimmed means and sample quantiles and functions thereof. This article is devoted to theory and applications of L -statistics for repeated measurements data, wherein the measurements on the same subject are dependent and the measurements from different subjects are independent. This article has three main goals: (a) Show that the L -statistics are asymptotically normal for repeated measurements data. (b) Present three statistical applications of this result, namely, location estimation using trimmed means, quantile estimation and construction of tolerance intervals. (c) Obtain a Bahadur representation for sample quantiles. These results are generalizations of similar results for independently and identically distributed data. The practical usefulness of these results is illustrated by analyzing a real data set involving measurement of systolic blood pressure. The properties of the proposed point and interval estimators are examined via simulation.

Effects of supplements that contain increasing amounts of metabolizable protein with or without Ca-propionate salt on postpartum interval and nutrient partitioning in young beef cows.

PubMed

Waterman, R C; Sawyer, J E; Mathis, C P; Hawkins, D E; Donart, G B; Petersen, M K

2006-02-01

Cattle grazing winter range forages exhibit interannual variation in response to supplementation. This variation may be mediated by circulating concentrations and subsequent metabolism of glucose, which are influenced by forage quality and availability. A study conducted at the Corona Range and Livestock Research Center during 2 dry years evaluated responses of young postpartum beef cows (n = 51, initial BW = 408 +/- 3 kg, and BCS = 5.1 +/- 0.04 in year 1; n = 36, initial BW = 393 +/- 4 kg, and BCS = 4.5 +/- 0.05 in year 2) to supplements that met or exceeded metabolizable protein (MP) requirements. Supplements were fed at 908 g/d per cow and provided 327 g of CP, 118 g of ruminally undegradable protein (RUP), and 261 g of MP from RUP (RMP), calculated to meet the MP requirement; 327 g of CP, 175 g of RUP, and 292 g of MP from RUP (RMP+), which supplied 31 g of excess MP; or 327 g of CP, 180 g of RUP, 297 g of MP from RUP, and 100 g of propionate salt (NutroCal, Kemin Industries, Inc., Des Moines, IA; (RMP+)P), which supplied 36 g of excess MP. Body weights were recorded once every 2 wk, and blood samples were collected 1x/wk in year 1 and 2x/wk in year 2 for 100 d postpartum. Postpartum anestrous was evaluated by progesterone from weekly blood samples, and pregnancy was confirmed by rectal palpation at weaning. As MP from RUP with or without propionate increased, a decrease (P = 0.03) was observed in postpartum interval; however, differences in pregnancy percentage (P = 0.54) were not influenced by treatments. We hypothesized that additional AA from RUP along with propionate would increase supply of glucogenic precursors and, therefore, glucogenic potential of the diet. Therefore, a postpartum glucose tolerance test was conducted near the nadir of cow BW to evaluate the rate of glucose clearance. Glucose tolerance tests showed that (RMP+)- or (RMP+)P-supplemented cows had greater (P = 0.03) rates of glucose clearance, which might have influenced the observed abbreviation of the postpartum interval. A glucose tolerance test conducted at the end of supplemental treatments revealed no differences in glucose clearance (P = 0.47) among previously supplemented cows. These data suggest that not only vegetative quality, duration of lactation, and season of grazing, but also type of supplementation may play a pivotal role in the young postpartum beef cow's ability to respond and incorporate nutrients into insulin-sensitive tissues.

Biosystematics, genetics and upper temperature tolerance of Gigartina teedii (Rhodophyta) from the Atlantic and Mediterranean

NASA Astrophysics Data System (ADS)

Guiry, M. D.; Tripodi, G.; Lüning, K.

1987-09-01

Plants of Gigartina teedii from the mediterranean isolated into laboratory culture showed Polysiphonia-type life histories with consistent formation of dioecious gametangial plants, as previously reported for Atlantic isolates. Male and female plants from the Atlantic and Mediterranean were almost completely compatible in terms of cystocarp formation on female plants, and carpospores from positive crosses always formed plants that released viable tetraspores. Sex-linked inheritance of branching pattern was found in all strains, but showed varying degrees of expression. Female plants were more branched than male plants and it is suggested that this may be an adaptation for spermatial capture. G. teedii plants showed differences in morphology in culture that are considered to be genetically-based. Preliminary studies of tip elongation showed that Mediterranean strains may have up to three times the elongation rates of Atlantic strains at 15°C,bar 8. Such genetic variation in fully-interbreeding strains suggests that populations of this species in the Atlantic and Mediterranean are genecodemic. All strains showed an upper temperature tolerance of 31°C when tested at 1°C intervals from 29—34°C. An upper temperature tolerance of 31 32°C was found for the related species G. intermedia from Korea and Japan, but G. johnstonii from the Gulf of California showed an upper tolerance of 32 33°C.

A methodology for testing fault-tolerant software

NASA Technical Reports Server (NTRS)

Andrews, D. M.; Mahmood, A.; Mccluskey, E. J.

1985-01-01

A methodology for testing fault tolerant software is presented. There are problems associated with testing fault tolerant software because many errors are masked or corrected by voters, limiter, or automatic channel synchronization. This methodology illustrates how the same strategies used for testing fault tolerant hardware can be applied to testing fault tolerant software. For example, one strategy used in testing fault tolerant hardware is to disable the redundancy during testing. A similar testing strategy is proposed for software, namely, to move the major emphasis on testing earlier in the development cycle (before the redundancy is in place) thus reducing the possibility that undetected errors will be masked when limiters and voters are added.

Ability of an alkali-tolerant mutant strain of the microalga Chlorella sp. AT1 to capture carbon dioxide for increasing carbon dioxide utilization efficiency.

PubMed

Kuo, Chiu-Mei; Lin, Tsung-Hsien; Yang, Yi-Chun; Zhang, Wen-Xin; Lai, Jinn-Tsyy; Wu, Hsi-Tien; Chang, Jo-Shu; Lin, Chih-Sheng

2017-11-01

An alkali-tolerant Chlorella sp. AT1 mutant strain was screened by NTG mutagenesis. The strain grew well in pH 6-11 media, and the optimal pH for growth was 10. The CO 2 utilization efficiencies of Chlorella sp. AT1 cultured with intermittent 10% CO 2 aeration for 10, 20 and 30min at 3-h intervals were approximately 80, 42 and 30%, respectively. In alkaline medium (pH=11) with intermittent 10% CO 2 aeration for 30min at 3-, 6- and 12-h intervals, the medium pH gradually changed to 10, and the biomass productivities of Chlorella sp. AT1 were 0.987, 0.848 and 0.710gL -1 d -1 , respectively. When Chlorella sp. AT1 was aerated with 10% CO 2 intermittently for 30min at 3-h intervals in semi-continuous cultivation for 21days, the biomass concentration and biomass productivity were 4.35gL -1 and 0.726gL -1 d -1 , respectively. Our results show that CO 2 utilization efficiency can be markedly increased by intermittent CO 2 aeration and alkaline media as a CO 2 -capturing strategy for alkali-tolerant microalga cultivation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Time-dependent relation between smoking cessation and improved exercise tolerance in apparently healthy middle-age men and women.

PubMed

Berkovitch, Anat; Kivity, Shaye; Klempfner, Robert; Segev, Shlomo; Milwidsky, Assi; Goldenberg, Ilan; Sidi, Yechezkel; Maor, Elad

2015-06-01

Smoking is an independent cardiovascular risk factor and correlates with reduced exercise tolerance. However, data on the time dependent effect of smoking cessation on exercise tolerance are limited. We investigated 17,115 men and women who were annually screened at the Institute for Medical Screening of the Chaim Sheba Medical Centre. All subjects had their smoking status documented and performed an exercise stress testing (EST) according to Bruce protocol at each visit. Subjects were divided at baseline into four groups: active smokers (N = 2858), recent quitters (smoking cessation ≤2 years before baseline EST; N = 861), remote quitters (smoking cessation >2 years before the baseline EST; N = 3856) and never smokers (N = 9810). Baseline and follow up EST duration were compared among the four groups. Recent quitters demonstrated a 2.4-fold improvement in their EST duration compared with active smokers (improvement of 24 ± 157 vs. 10 ± 157 s, respectively, p = 0.02). Multivariate logistic regression showed that recent quitters were 26% more likely to improve their exercise tolerance compared with active smokers (95% confidence interval (CI) 1.08-1.47, p = 0.003). Assessing smoking status as a time-dependent covariate during four consecutive visits demonstrated that recent quitters were 17% more likely to improve their exercise tolerance compared with active smokers (95% CI 1.02-1.34, p = 0.02), with a less pronounced benefit among remote quitters (hazard ratio = 1.11, 95% CI 1.02-1.21; p = 0.01). Smoking cessation is independently associated with improved exercise tolerance. The benefits of smoking cessation are evident within the first two years of abstinence. © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Spaceflight alters autonomic regulation of arterial pressure in humans

NASA Technical Reports Server (NTRS)

Fritsch-Yelle, Janice M.; Charles, John B.; Jones, Michele M.; Beightol, Larry A.; Eckberg, Dwain L.

1994-01-01

Spaceflight is associated with decreased orthostatic tolerance after landing. Short-duration spaceflight (4 - 5 days) impairs one neutral mechanism: the carotid baroreceptor-cardiac reflex. To understand the effects of longer-duration spaceflight on baroreflex function, we measured R-R interval power spectra, antecubital vein plasma catecholamine levels, carotid baroreceptor-cardiac reflex responses, responses to Valsalva maneuvers, and orthostatic tolerance in 16 astronauts before and after shuttle missions lasting 8 - 14 days. We found the following changes between preflight and landing day: (1) orthostatic tolerance decreased; (2) R-R interval spectral power in the 0.05- to 0.15-Hz band increased; (3) plasma norepinephrine and epinephrine levels increased; (4) the slope, range, and operational point of the carotid baroreceptor cardiac reflex response decreased; and (5) blood pressure and heart rate responses to Valsalva maneuvers were altered. Autonomic changes persisted for several days after landing. These results provide further evidence of functionally relevent reductions in parasympathetic and increases in sympathetic influences on arterial pressure control after spaceflight.

Atlantic DIP: high prevalence of abnormal glucose tolerance post partum is reduced by breast-feeding in women with prior gestational diabetes mellitus.

PubMed

O'Reilly, Michael W; Avalos, Gloria; Dennedy, Michael C; O'Sullivan, Eoin P; Dunne, Fidelma

2011-12-01

Gestational diabetes (GDM) is associated with adverse fetal and maternal outcomes, and identifies women at risk of future type 2 diabetes mellitus (T2DM). Breast-feeding may improve post partum maternal glucose tolerance. Our objective was to identify the prevalence of post partum dysglycemia after GDM, to delineate associated factors and to examine the effect of lactation on post partum glucose tolerance. We compared post partum 75 g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT) in five regional centers. Breast-feeding data was collected at time of OGTT. Methods Post partum OGTT results were classified as normal (fasting plasma glucose (FPG) <5.6 mmol/l, 2 h <7.8 mmol/l) and abnormal (impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2 h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG ≥7 mmol/l±2 h glucose ≥11.1 mmol/l). Binary logistic regression was used to identify factors predictive of persistent hyperglycemia. Five hundred and twenty women were tested; six (2.7%) with NGT in pregnancy had post partum dysglycemia compared with 57 (19%) with GDM in index pregnancy (P<0.001). Non-European ethnicity (odds ratio (OR) 3.40; 95% confidence interval (CI) 1.45-8.02, P=0.005), family history of T2DM (OR 2.14; 95% CI 1.06-4.32, P=0.034), and gestational insulin use (OR 2.62; 95% CI 1.17-5.87, P=0.019) were associated with persistent dysglycemia. The prevalence of persistent hyperglycemia was significantly lower in women who breast-fed vs bottle-fed post partum (8.2 vs 18.4%, P<0.001). Non-European ethnicity, gestational insulin use, family history of T2DM, and elevated body mass index were associated with persistent dysglycemia after GDM. Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.

PubMed

Ditre, Joseph W; Heckman, Bryan W; Zale, Emily L; Kosiba, Jesse D; Maisto, Stephen A

2016-07-01

Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.

Local rollback for fault-tolerance in parallel computing systems

DOEpatents

Blumrich, Matthias A [Yorktown Heights, NY; Chen, Dong [Yorktown Heights, NY; Gara, Alan [Yorktown Heights, NY; Giampapa, Mark E [Yorktown Heights, NY; Heidelberger, Philip [Yorktown Heights, NY; Ohmacht, Martin [Yorktown Heights, NY; Steinmacher-Burow, Burkhard [Boeblingen, DE; Sugavanam, Krishnan [Yorktown Heights, NY

2012-01-24

A control logic device performs a local rollback in a parallel super computing system. The super computing system includes at least one cache memory device. The control logic device determines a local rollback interval. The control logic device runs at least one instruction in the local rollback interval. The control logic device evaluates whether an unrecoverable condition occurs while running the at least one instruction during the local rollback interval. The control logic device checks whether an error occurs during the local rollback. The control logic device restarts the local rollback interval if the error occurs and the unrecoverable condition does not occur during the local rollback interval.

Using Quality of Life Measures in a Phase I Clinical Trial of Noni in Patients with Advanced Cancer to Select a Phase II Dose

PubMed Central

Issell, Brian F.; Gotay, Carolyn C.; Pagano, Ian; Franke, A. Adrian

2015-01-01

Purpose We conducted a Phase I study of noni in patients with advanced cancer. Quality of life measures were examined as an alternate way to select a Phase II dose of this popular dietary supplement. Patients and Methods Starting at two capsules twice daily (2 grams), the dose suggested for marketed products, dose levels were escalated by 2 grams daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed QLQ-C30 Quality of Life, and the Brief Fatigue Inventory (BFI), questionnaires at baseline and at four week intervals. Scopoletin was measured in blood and urine collected at baseline and at approximately four week intervals. Results Fifty-one patients were enrolled at seven dose levels. Seven capsules four times daily (14 grams) was the maximum tolerated dose. No dose limiting toxicity was found but four of eight patients at this level withdrew from the study due to the challenges of ingesting so many capsules. There was a dose response for self reported physical functioning and the control of pain and fatigue. Patients taking four capsules four times daily experienced less fatigue than patients taking lower or higher doses. A relationship between noni dose and blood and urinary scopoletin concentrations was found. Conclusion Measuring quality of life to determine a dose for subsequent Phase II testing is feasible. A noni dose of four capsules four times daily (8 grams) is recommended for Phase II testing where controlling fatigue and maintaining physical function is the efficacy of interest. Scopoletin is a measurable noni ingredient for pharmacokinetic studies in patients with cancer. PMID:22435516

Association between physical exercise and quality of erection in men with ischaemic heart disease and erectile dysfunction subjected to physical training.

PubMed

Kałka, Dariusz; Domagała, Zygmunt; Dworak, Jacek; Womperski, Krzysztof; Rusiecki, Lesław; Marciniak, Wojciech; Adamus, Jerzy; Pilecki, Witold

2013-01-01

In addition to a beneficial effect on exercise tolerance and an associated reduction of global cardiovascular risk, modification of physical activity has a positive effect on the quality of life, reducing, among other things, the severity of erectile dysfunction (ED). The specific nature of sexual activity, which combines the need to maintain appropriate exercise tolerance and good erection quality, prompted us to evaluate the association between exercise tolerance and severity of ED in an intervention group of subjects with ischaemic heart disease (IHD) and ED in the context of cardiac rehabilitation (CR). A total of 138 men treated invasively for IHD (including 99 treated with percutaneous coronary intervention and 39 treated with coronary artery bypass grafting) who scored 21 or less in the initial IIEF-5 test were investigated. Subjects were randomised into two groups. The study group included 103 subjects (mean age 62.07 ± 8.59 years) who were subjected to a CR cycle. The control group included 35 subjects (mean age 61.43 ± 8.81 years) who were not subjected to any CR. All subjects filled out an initial and final IIEF-5 questionnaire and were evaluated twice with a treadmill exercise test. The CR cycle was carried out for a period of 6 months and included interval endurance training on a cycle ergometer (three times a week) and general fitness exercises and resistance training (twice a week). The CR cycle in the study group resulted in a statistically significant increase in exercise tolerance (7.15 ± 1.69 vs. 9.16 ± 1.84 METs,p < 0.05) and an increase in erection quality (12.51 ± 5.98 vs. 14.39 ± 6.82, p < 0.05) which was not observed in the control group. A significant effect of age on a progressive decrease in exercise tolerance and erection quality was found in the study group. Exercise tolerance and erection quality were also negatively affected by hypertension and smoking. A significant correlation between exercise tolerance and erection quality prior to the rehabilitation cycle indicates better erection quality in patients with better effort tolerance. The improvement in exercise tolerance did not correlate significantly with initial exercise tolerance or age of the subjects. In contrast, a significantly higher increase in erection quality was observed in younger subjects with the lowest baseline severity of ED.The relative increase in exercise tolerance in the group subjected to CR was significantly higher than the relative increase in erection quality but these two effects were not significantly correlated with each other. 1. In subjects with IHD and ED, erection quality is significantly correlated with exercise tolerance. 2. Exercise training had a positive effect on both exercise tolerance and erection quality but the size of these two effects was different and they ran independently of each other.

[Comparative studies on the bioavailability of nicergoline from two different steady-state preparations].

PubMed

Kohlenberg-Müller, K; Meier, D H; Kunz, K; Wauschkuhn, C H; Schaffler, K

1991-07-01

Comparative Studies on the Bioavailability of Nicergoline from Two Different Preparations in Steady State The bioavailability of nicergoline (CAS 27848-84-6) in a new 30 mg tablet and a 10 mg dragee formulation (Sermion) was evaluated under steady state conditions in 18 healthy male volunteers between the age of 21 and 37 years. During the run-in phase, the volunteers received on 7 consecutive days 30 mg nicergoline either 1 x 30 mg/d tablet (test substance) or 3 x 10 mg dragees (reference). On day 8, after intake of 1 x 30 mg in a 24 h interval or 1 x 10 mg in a 8 h interval respectively, the plasma concentrations of the nicergoline metabolite 10-methoxy-6-methyl-ergoline-8 beta-methanol (MDL) were measured. The area under the plasma concentrations in the 24 h interval after administering the 30 mg tablet was not 3 times greater as to be expected; it was by a factor of 4 significantly greater than the area under the curve of the 10 mg dragee in the 8 h interval. Therefore, nicergoline has a higher availability in the 30 mg tablet than in the 10 mg dragee form. Both formulations were equally well tolerated.

Resonant ultrasound spectroscopy

DOEpatents

Migliori, Albert

1991-01-01

A resonant ultrasound spectroscopy method provides a unique characterization of an object for use in distinguishing similar objects having physical differences greater than a predetermined tolerance. A resonant response spectrum is obtained for a reference object by placing excitation and detection transducers at any accessible location on the object. The spectrum is analyzed to determine the number of resonant response peaks in a predetermined frequency interval. The distribution of the resonance frequencies is then characterized in a manner effective to form a unique signature of the object. In one characterization, a small frequency interval is defined and stepped though the spectrum frequency range. Subsequent objects are similarly characterized where the characterizations serve as signatures effective to distinguish objects that differ from the reference object by more than the predetermined tolerance.

The combination of arbuscular mycorrhizal fungi inoculation (Glomus versiforme) and 28-homobrassinolide spraying intervals improves growth by enhancing photosynthesis, nutrient absorption, and antioxidant system in cucumber (Cucumis sativus L.) under salinity.

PubMed

Ahmad, Husain; Hayat, Sikandar; Ali, Muhammad; Liu, Tao; Cheng, Zhihui

2018-06-01

Salinity is one of the major obstacles in the agriculture industry causing huge losses in productivity. Several strategies such as plant growth regulators with arbuscular mycorrhizal fungi (AMF) have been used to decrease the negative effects of salt stress. In our experiment, 28-homobrassinolide (HBL) with spraying intervals was combined with AMF ( Glomus versiforme ) in cucumber cultivars Jinyou 1 # (salt sensitive) and (Changchun mici, in short, CCMC, salt tolerant) under NaCl (100 mmol/L). Studies have documented that the foliar application of HBL and AMF colonization can enhance tolerance to plants under stress conditions. However, the mechanism of the HBL spraying intervals after 15 and 30 days in combination with AMF in cucumber under salt stress is still unknown. Our results revealed that the HBL spraying interval after 15 days in combination with AMF resulted in improved growth, photosynthesis, and decreased sodium toxicity under NaCl. Moreover, the antioxidant enzymes SOD (superoxide dismutase; EC 1.15.1.1) and POD activity (peroxidase; EC 1.11.1.7) showed a gradual increase after every 10 days, while the CAT (catalase; EC 1.11.1.6) increased after 30 days of salt treatments in both cultivars. This research suggests that the enhanced tolerance to salinity was mainly related to elevated levels of antioxidant enzymes and lower uptake of Na + , which lowers the risk of ion toxicity and decreases cell membrane damage.

Genome-wide QTL mapping of saltwater tolerance in sibling species of Anopheles (malaria vector) mosquitoes

PubMed Central

Smith, H A; White, B J; Kundert, P; Cheng, C; Romero-Severson, J; Andolfatto, P; Besansky, N J

2015-01-01

Although freshwater (FW) is the ancestral habitat for larval mosquitoes, multiple species independently evolved the ability to survive in saltwater (SW). Here, we use quantitative trait locus (QTL) mapping to investigate the genetic architecture of osmoregulation in Anopheles mosquitoes, vectors of human malaria. We analyzed 1134 backcross progeny from a cross between the obligate FW species An. coluzzii, and its closely related euryhaline sibling species An. merus. Tests of 2387 markers with Bayesian interval mapping and machine learning (random forests) yielded six genomic regions associated with SW tolerance. Overlap in QTL regions from both approaches enhances confidence in QTL identification. Evidence exists for synergistic as well as disruptive epistasis among loci. Intriguingly, one QTL region containing ion transporters spans the 2Rop chromosomal inversion that distinguishes these species. Rather than a simple trait controlled by one or a few loci, our data are most consistent with a complex, polygenic mode of inheritance. PMID:25920668

Assessment of tolerance to the effects of methamphetamine on daytime and nighttime activity evaluated with actigraphy in rhesus monkeys.

PubMed

Berro, Laís F; Andersen, Monica L; Howell, Leonard L

2017-08-01

Methamphetamine is one of the most largely consumed illicit drugs, and its use is associated with abuse liability and several adverse health effects, such as sleep impairment. Importantly, sleep quality can influence addiction treatment outcomes. Evidence suggests that tolerance can develop to the sleep-disrupting effects of stimulant drugs. The aim of the present study was to investigate the development of tolerance to the actigraphy-based sleep-disrupting and stimulant effects of methamphetamine self-administration in rhesus monkeys. Methamphetamine (0.03 mg/kg/inf, i.v.) self-administration was carried out following three different protocols: 14 consecutive days of self-administration, 5 days/week for 3 weeks, with a 2-day interval between 5-day blocks of self-administration, and 3 days/week for 3 weeks, with a 4-day interval between 3-day blocks of self-administration. Daytime activity and activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline parameters) and throughout each protocol. Methamphetamine self-administration markedly disrupted sleep-like measures and increased daytime activity. Tolerance developed to those effects with repeated methamphetamine intake exceeding five consecutive days. Inclusion of washout periods (2 or 4 days) between blocks of methamphetamine self-administration attenuated the development of tolerance, with longer breaks from methamphetamine intake being more effective in maintaining the sleep-disrupting and stimulant effects of methamphetamine. Tolerance can develop to the stimulant and sleep-disrupting effects of methamphetamine self-administration. Interruption of drug intake extends the effects of methamphetamine on sleep-like measures and daytime activity.

7 CFR 801.9 - Tolerances for test weight apparatuses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PERFORMANCE REQUIREMENTS FOR GRAIN INSPECTION EQUIPMENT § 801.9 Tolerances for test weight apparatuses. The maintenance tolerances for test weight per bushel apparatuses used in performing official inspection services... 7 Agriculture 7 2011-01-01 2011-01-01 false Tolerances for test weight apparatuses. 801.9 Section...

7 CFR 801.9 - Tolerances for test weight apparatuses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PERFORMANCE REQUIREMENTS FOR GRAIN INSPECTION EQUIPMENT § 801.9 Tolerances for test weight apparatuses. The maintenance tolerances for test weight per bushel apparatuses used in performing official inspection services... 7 Agriculture 7 2010-01-01 2010-01-01 false Tolerances for test weight apparatuses. 801.9 Section...

Active fault tolerant control based on interval type-2 fuzzy sliding mode controller and non linear adaptive observer for 3-DOF laboratory helicopter.

PubMed

Zeghlache, Samir; Benslimane, Tarak; Bouguerra, Abderrahmen

2017-11-01

In this paper, a robust controller for a three degree of freedom (3 DOF) helicopter control is proposed in presence of actuator and sensor faults. For this purpose, Interval type-2 fuzzy logic control approach (IT2FLC) and sliding mode control (SMC) technique are used to design a controller, named active fault tolerant interval type-2 Fuzzy Sliding mode controller (AFTIT2FSMC) based on non-linear adaptive observer to estimate and detect the system faults for each subsystem of the 3-DOF helicopter. The proposed control scheme allows avoiding difficult modeling, attenuating the chattering effect of the SMC, reducing the rules number of the fuzzy controller. Exponential stability of the closed loop is guaranteed by using the Lyapunov method. The simulation results show that the AFTIT2FSMC can greatly alleviate the chattering effect, providing good tracking performance, even in presence of actuator and sensor faults. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Personality traits in companion dogs-Results from the VIDOPET.

PubMed

Turcsán, Borbála; Wallis, Lisa; Virányi, Zsófia; Range, Friederike; Müller, Corsin A; Huber, Ludwig; Riemer, Stefanie

2018-01-01

Individual behavioural differences in pet dogs are of great interest from a basic and applied research perspective. Most existing dog personality tests have specific (practical) goals in mind and so focused only on a limited aspect of dogs' personality, such as identifying problematic (aggressive or fearful) behaviours, assessing suitability as working dogs, or improving the results of adoption. Here we aimed to create a comprehensive test of personality in pet dogs that goes beyond traditional practical evaluations by exposing pet dogs to a range of situations they might encounter in everyday life. The Vienna Dog Personality Test (VIDOPET) consists of 15 subtests and was performed on 217 pet dogs. A two-step data reduction procedure (principal component analysis on each subtest followed by an exploratory factor analysis on the subtest components) yielded five factors: Sociability-obedience, Activity-independence, Novelty seeking, Problem orientation, and Frustration tolerance. A comprehensive evaluation of reliability and validity measures demonstrated excellent inter- and intra-observer reliability and adequate internal consistency of all factors. Moreover the test showed good temporal consistency when re-testing a subsample of dogs after an average of 3.8 years-a considerably longer test-retest interval than assessed for any other dog personality test, to our knowledge. The construct validity of the test was investigated by analysing the correlations between the results of video coding and video rating methods and the owners' assessment via a dog personality questionnaire. The results demonstrated good convergent as well as discriminant validity. To conclude, the VIDOPET is not only a highly reliable and valid tool for measuring dog personality, but also the first test to show consistent behavioural traits related to problem solving ability and frustration tolerance in pet dogs.

Personality traits in companion dogs—Results from the VIDOPET

PubMed Central

Wallis, Lisa; Virányi, Zsófia; Range, Friederike; Müller, Corsin A.; Huber, Ludwig; Riemer, Stefanie

2018-01-01

Individual behavioural differences in pet dogs are of great interest from a basic and applied research perspective. Most existing dog personality tests have specific (practical) goals in mind and so focused only on a limited aspect of dogs’ personality, such as identifying problematic (aggressive or fearful) behaviours, assessing suitability as working dogs, or improving the results of adoption. Here we aimed to create a comprehensive test of personality in pet dogs that goes beyond traditional practical evaluations by exposing pet dogs to a range of situations they might encounter in everyday life. The Vienna Dog Personality Test (VIDOPET) consists of 15 subtests and was performed on 217 pet dogs. A two-step data reduction procedure (principal component analysis on each subtest followed by an exploratory factor analysis on the subtest components) yielded five factors: Sociability-obedience, Activity-independence, Novelty seeking, Problem orientation, and Frustration tolerance. A comprehensive evaluation of reliability and validity measures demonstrated excellent inter- and intra-observer reliability and adequate internal consistency of all factors. Moreover the test showed good temporal consistency when re-testing a subsample of dogs after an average of 3.8 years—a considerably longer test-retest interval than assessed for any other dog personality test, to our knowledge. The construct validity of the test was investigated by analysing the correlations between the results of video coding and video rating methods and the owners’ assessment via a dog personality questionnaire. The results demonstrated good convergent as well as discriminant validity. To conclude, the VIDOPET is not only a highly reliable and valid tool for measuring dog personality, but also the first test to show consistent behavioural traits related to problem solving ability and frustration tolerance in pet dogs. PMID:29634747

Exercise Versus +Gz Acceleration Training

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Simonson, S. R.; Stocks, J. M.; Evans, J. M.; Knapp, C. F.; Dalton, Bonnie P. (Technical Monitor)

2002-01-01

Decreased working capacity and "orthostatic" intolerance are two major problems for astronauts during and after landing from spaceflight in a return vehicle. The purpose was to test the hypotheses that (1) supine-passive-acceleration training, supine-interval-exercise plus acceleration training, and supine exercise plus acceleration training will improve orthostatic tolerance (OT) in ambulatory men; and that (2) addition of aerobic exercise conditioning will not influence this enhanced OT from that of passive-acceleration training. Seven untrained men (24-38 yr) underwent 3 training regimens (30 min/d x 5d/wk x 3wk on the human-powered centrifuge - HPC): (a) Passive acceleration (alternating +1.0 Gz to 50% Gzmax); (b) Exercise acceleration (alternating 40% - 90% V02max leg cycle exercise plus 50% of HPCmax acceleration); and (c) Combined intermittent exercise-acceleration at 40% to 90% HPCmax. Maximal supine exercise workloads increased (P < 0.05) by 8.3% with Passive, by 12.6% with Exercise, and by 15.4% with Combined; but maximal V02 and HR were unchanged in all groups. Maximal endurance (time to cessation) was unchanged with Passive, but increased (P < 0.05) with Exercise and Combined. Resting pre-tilt HR was elevated by 12.9% (P < 0.05) only after Passive training, suggesting that exercise training attenuated this HR response. All resting pre-tilt blood pressures (SBP, DBP, MAP) were not different pre- vs. post-training. Post-training tilt-tolerance time and HR were increased (P < 0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training attenuated the increased Passive tilt tolerance. Resting (pre-tilt) and post-tilt cardiac R-R interval, stroke volume, end-diastolic volume, and cardiac output were all uniformly reduced (P < 0.05) while peripheral resistance was uniformly increased (P < 0.05) pre-and post-training for the three regimens indicating no effect of any training regimen on those cardiovascular variables. Plasma volume (% delta) was uniformly decreased by 8% to 14% (P < 0.05) at tilt-tolerance pre- vs. post-training for all regimens indicating no effect of these training regimens on the level of vascular fluid shifts.

Micro-ribonucleic acid-binding site variants of type 2 diabetes candidate loci predispose to gestational diabetes mellitus in Chinese Han women.

PubMed

Wang, Xiaojing; Li, Wei; Ma, Liangkun; Ping, Fan; Liu, Juntao; Wu, Xueyan; Mao, Jiangfeng; Wang, Xi; Nie, Min

2018-01-20

Emerging evidence has suggested that the genetic background of gestational diabetes mellitus (GDM) was analogous to type 2 diabetes mellitus. In contrast to type 2 diabetes mellitus, the genetic studies for GDM were limited. Accordingly, the aim of the present study was to extensively explore the influence of micro-ribonucleic acid-binding single-nucleotide polymorphisms (SNPs) in type 2 diabetes mellitus candidate loci on GDM susceptibility in Chinese. A total of 839 GDM patients and 900 controls were enrolled. Six micro-ribonucleic acid-binding SNPs were selected from 30 type 2 diabetes mellitus susceptibility loci and genotyped using TaqMan allelic discrimination assays. The minor allele of three SNPs, PAX4 rs712699 (OR 1.366, 95% confidence interval 1.021-1.828, P = 0.036), KCNB1 rs1051295 (OR 1.579, 95% confidence interval 1.172-2.128, P = 0.003) and MFN2 rs1042842 (OR 1.398, 95% confidence interval 1.050-1.862, P = 0.022) were identified to significantly confer higher a risk of GDM in the additive model. The association between rs1051295 and increased fasting plasma glucose (b = 0.006, P = 0.008), 3-h oral glucose tolerance test plasma glucose (b = 0.058, P = 0.025) and homeostatic model assessment of insulin resistance (b = 0.065, P = 0.017) was also shown. Rs1042842 was correlated with higher 3-h oral glucose tolerance test plasma glucose (b = 0.056, P = 0.028). However, no significant correlation between the other included SNPs (LPIN1 rs1050800, VPS26A rs1802295 and NLRP3 rs10802502) and GDM susceptibility were observed. The present findings showed that micro-ribonucleic acid-binding SNPs in type 2 diabetes mellitus candidate loci were also associated with GDM susceptibility, which further highlighted the similar genetic basis underlying GDM and type 2 diabetes mellitus. © 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Graded Aerobic Treadmill Testing in Adolescent Traumatic Brain Injury Patients.

PubMed

Cordingley, Dean M; Girardin, Richard; Morissette, Marc P; Reimer, Karen; Leiter, Jeff; Russell, Kelly; Ellis, Michael J

2017-11-01

To examine the safety and tolerability of clinical graded aerobic treadmill testing in recovering adolescent moderate and severe traumatic brain injury (TBI) patients referred to a multidisciplinary pediatric concussion program. We completed a retrospective case series of two moderate and five severe TBI patients (mean age, 17.3 years) who underwent initial Buffalo Concussion Treadmill Testing at a mean time of 71.6 days (range, 55-87) postinjury. Six patients completed one graded aerobic treadmill test each and one patient underwent initial and repeat testing. There were no complications. Five initial treadmill tests were completely tolerated and allowed an accurate assessment of exercise tolerance. Two initial tests were terminated early by the treatment team because of neurological and cardiorespiratory limitations. As a result of testing, two patients were cleared for aerobic exercise as tolerated and four patients were treated with individually tailored submaximal aerobic exercise programs resulting in subjective improvement in residual symptoms and/or exercise tolerance. Repeat treadmill testing in one patient performed after 1 month of treatment with submaximal aerobic exercise prescription was suggestive of improved exercise tolerance. One patient was able to tolerate aerobic exercise following surgery for posterior glottic stenosis. Preliminary results suggest that graded aerobic treadmill testing is a safe, well tolerated, and clinically useful tool to assess exercise tolerance in appropriately selected adolescent patients with TBI. Future prospective studies are needed to evaluate the effect of tailored submaximal aerobic exercise prescription on exercise tolerance and patient outcomes in recovering adolescent moderate and severe TBI patients.

[New visual field testing possibilities (a preliminary report)].

PubMed

Erichev, V P; Ermolaev, A P; Antonov, A A; Grigoryan, G L; Kosova, D V

2018-01-01

There are currently no portable mobile perimeters that allow visual field testing outside ophthalmologist's examination rooms. To develop a mobile perimetry technique based on use of a virtual reality headset (VR). The study involved 26 patients (30 eyes) with II-III stage primary open-angle glaucoma (POAG) with compensated IOP. Perimetry was performed for each patient twice - on Humphrey analyzer (test 30-2, 76 points) and employing similar strategy on a perimeter integrated into VR headset (Total Vision, Russia). Visual field testing was performed with an interval from 1 hour to 3 days. The results were comparatively analyzed. Patients tolerated the examination well. Comparative analysis of preliminary perimetry results obtained with both methods showed high degree of identity, so the results were concluded to be comparable. By visually isolating the wearer, VR headset achieves elimination of distractions and stable light conditions for visual field testing. The headset-perimeter is compact, mobile, easily transportable, can be used in the work of visiting medical teams and for examination at home.

Endoscopic Management of Idiopathic Subglottic Stenosis.

PubMed

Shabani, Sepehr; Hoffman, Matthew R; Brand, William T; Dailey, Seth H

2017-02-01

To describe a homogeneous idiopathic subglottic stenosis (ISS) population undergoing endoscopic balloon dilation and evaluate factors affecting inter-dilation interval (IDI). Retrospective review of 37 patients. Co-morbidity prevalence versus normal population was evaluated using chi-square tests. Correlations were evaluated using Pearson product moment tests. Independent samples t tests/rank sum tests assessed differences between groups of interest. All patients were female aged 45.9 ± 15.4 years at diagnosis. Four required a tracheotomy during management. Most prevalent co-morbidity was gastroesophageal reflux disease (GERD) (64.9%; P = .036). Body mass indices (BMI) at first and most recent dilation were 29.8 and 30.8 ( P = .564). Degree of stenosis before first dilation was 53 ± 14%. Patients underwent 3.8 ± 1.8 dilations (range, 1-11). Average IDI was 635 ± 615 days (range, 49-3130 days), including 556 ± 397 days for patients receiving concomitant steroid injection and 283 ± 36 for those who did not ( P = .079). Inter-dilation interval was not correlated with BMI ( r = 0.0486; P = .802) or number of co-morbidities ( r = -0.225, P = .223). Most patients with ISS can be managed endoscopically, and IDI may be increased with steroid injection. Gastroesophageal reflux disease is a common co-morbidity. Body mass index did not change over time despite potential effects on exercise tolerance; BMI did not affect IDI. Methods to determine optimal timing for next intervention are warranted.

Efficacy and tolerability of six-week extended dosing interval with tocilizumab therapy in a prospective cohort as remission maintenance in patients with rheumatoid arthritis.

PubMed

Kikuchi, Jun; Kondo, Tsuneo; Shibata, Akiko; Sakai, Ryota; Okada, Yusuke; Chino, Kentaro; Okuyama, Ayumi; Kurasawa, Takahiko; Takei, Hirofumi; Amano, Koichi

2018-05-01

To prospectively evaluate the efficacy and tolerability of a six-week extended dosing interval with tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) in sustained remission. Patients who received over six doses of intravenous TCZ in clinical remission (disease activity score [DAS] 28 - erythrocyte sedimentation rate [ESR] ≤ 2.6) maintained over 3 months between December 2013 and December 2015 were included. Flare was defined as DAS28-ESR >3.2 at two consecutive visits. Twenty-five patients were enrolled; 87.5% achieved clinical remission at week 54 after six-week extension and 95.5% achieved a van der Heijde modified total Sharp score (ΔmTSS) ≤0.5. The Health Assessment Questionnaire Disability Index (HAQ-DI) did not increase during 54 weeks. HAQ-DI at baseline and ΔDAS28-ESR at week six positively correlated with increase in DAS28-ESR at week 54. ΔSwollen joint count at week six positively correlated with ΔmTSS at week 54. A total of 12 adverse events occurring in 10 patients did not lead to cessation of TCZ except for one case of recurrent lymphoproliferative disorder at week five. A six-week extended dosing interval of TCZ for patients with RA in sustained remission is proposed as an acceptable treatment option for maintaining efficacy and tolerability.

The Rectangle Target Plot: A New Approach to the Graphical Presentation of Accuracy of Systems for Self-Monitoring of Blood Glucose.

PubMed

Stephan, Peter; Schmid, Christina; Freckmann, Guido; Pleus, Stefan; Haug, Cornelia; Müller, Peter

2015-10-09

The measurement accuracy of systems for self-monitoring of blood glucose (SMBG) is usually analyzed by a method comparison in which the analysis results are displayed using difference plots or similar graphs. However, such plots become difficult to comprehend as the number of data points displayed increases. This article introduces a new approach, the rectangle target plot (RTP), which aims to provide a simplified and comprehensible visualization of accuracy data. The RTP is based on ISO 15197 accuracy evaluations of SMBG systems. Two-sided tolerance intervals for normally distributed data are calculated for absolute and relative differences at glucose concentrations <100 mg/dL and ≥100 mg/dL. These tolerance intervals provide an estimator of where a 90% proportion of results is found with a confidence level of 95%. Plotting these tolerance intervals generates a rectangle whose center indicates the systematic measurement difference of the investigated system relative to the comparison method. The size of the rectangle depends on the measurement variability. The RTP provides a means of displaying measurement accuracy data in a simple and comprehensible manner. The visualization is simplified by reducing the displayed information from typically 200 data points to just 1 rectangle. Furthermore, this allows data for several systems or several lots from 1 system to be displayed clearly and concisely in a single graph. © 2015 Diabetes Technology Society.

Combining gene expression and genetic analyses to identify candidate genes involved in cold responses in pea.

PubMed

Legrand, Sylvain; Marque, Gilles; Blassiau, Christelle; Bluteau, Aurélie; Canoy, Anne-Sophie; Fontaine, Véronique; Jaminon, Odile; Bahrman, Nasser; Mautord, Julie; Morin, Julie; Petit, Aurélie; Baranger, Alain; Rivière, Nathalie; Wilmer, Jeroen; Delbreil, Bruno; Lejeune-Hénaut, Isabelle

2013-09-01

Cold stress affects plant growth and development. In order to better understand the responses to cold (chilling or freezing tolerance), we used two contrasted pea lines. Following a chilling period, the Champagne line becomes tolerant to frost whereas the Terese line remains sensitive. Four suppression subtractive hybridisation libraries were obtained using mRNAs isolated from pea genotypes Champagne and Terese. Using quantitative polymerase chain reaction (qPCR) performed on 159 genes, 43 and 54 genes were identified as differentially expressed at the initial time point and during the time course study, respectively. Molecular markers were developed from the differentially expressed genes and were genotyped on a population of 164 RILs derived from a cross between Champagne and Terese. We identified 5 candidate genes colocalizing with 3 different frost damage quantitative trait loci (QTL) intervals and a protein quantity locus (PQL) rich region previously reported. This investigation revealed the role of constitutive differences between both genotypes in the cold responses, in particular with genes related to glycine degradation pathway that could confer to Champagne a better frost tolerance. We showed that freezing tolerance involves a decrease of expression of genes related to photosynthesis and the expression of a gene involved in the production of cysteine and methionine that could act as cryoprotectant molecules. Although it remains to be confirmed, this study could also reveal the involvement of the jasmonate pathway in the cold responses, since we observed that two genes related to this pathway were mapped in a frost damage QTL interval and in a PQL rich region interval, respectively. Copyright © 2013 Elsevier GmbH. All rights reserved.

Long-term tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. In this Phase III, multicentre, open-label study, women (aged 18-35 years) were randomised to EE/DRSP in the following regimens: flexible(MIB) (24-120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexible(MIB) regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexible(MIB), conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives.

A General theory of Signal Integration for Fault-Tolerant Dynamic Distributed Sensor Networks

DTIC Science & Technology

1993-10-01

related to a) the architecture and fault- tolerance of the distributed sensor network, b) the proper synchronisation of sensor signals, c) the...Computational complexities of the problem of distributed detection. 5) Issues related to recording of events and synchronization in distributed sensor...Intervals for Synchronization in Real Time Distributed Systems", Submitted to Electronic Encyclopedia. 3. V. G. Hegde and S. S. Iyengar "Efficient

De-labelling self-reported penicillin allergy within the emergency department through the use of skin tests and oral drug provocation testing.

PubMed

Marwood, Joseph; Aguirrebarrena, Gonzalo; Kerr, Stephen; Welch, Susan A; Rimmer, Janet

2017-10-01

Self-reported penicillin allergy is common among patients attending the ED, but is a poor predictor of true immunoglobulin E-mediated hypersensitivity to penicillin. We hypothesise that with a combination of skin testing and drug provocation testing, selected patients can be safely de-labelled of their allergy. This prospective study enrolled a sample of patients presenting to an urban academic ED between 2011 and 2016 with a self-reported allergy to penicillin. Standardised skin prick and intradermal testing with amoxicillin and both major and minor determinants of penicillin was performed in the department. If negative, testing was followed by a graded oral challenge of amoxicillin over 9 days. The primary end point was the allergy status of participants at the end of the study. A total of 100 patients (mean age 42; standard deviation 14 years; 54% women) completed the testing. Of these, 81% (95% confidence interval 71.9-88.2) showed no hypersensitivity to penicillin and were labelled non-allergic. The majority (16/19) of allergies were confirmed by skin testing, with three suspected allergies detected by the oral challenge. Women were more likely than men to have a true penicillin allergy, with odds ratio of 4.0 (95% confidence interval 1.23-13.2). There were no serious adverse events. Selected patients in the ED who self-report an allergy to penicillin can be safely tested there for penicillin allergy, using skin tests and oral drug provocation testing. This testing allows a significant de-labelling of penicillin allergy, with the majority of these patients able to tolerate penicillin without incident. © 2017 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Late effects of radiation on the lumbar spinal cord of guinea pigs: Re-treatment tolerance

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

Mason, K.A.; Withers, H.R.; Chiang, Chi-Shiun

Using a guinea pig model of lumbar myelopathy, various factors affecting the tolerance of spinal cord to irradiation were assessed: (a) extent of initial injury; (b) time interval between priming and test doses; and (c) animal age at the time of initial radiation treatment. A 3 cm section of lumbar spinal cord of guinea pigs was irradiated with fractionated doses of 4.5 Gy gamma rays given as 9 fractions per week. Guinea pigs were primed with 9 x 4.5 Gy in 7 days which is 60% of the ED[sub 50] for a continuous course of treatment. After 28 or 40more » weeks, animal were retreated with 6-14 fractions of 4.5 Gy. Animals were observed for 2 years following the priming dose and both the incidence and latency of myelopathy recorded. Young adult guinea pigs (8 wk old) showed both a decreased radiation tolerance and latency compared to old individuals (40 wk old). At 28 or 40 wk after 9 x 4.5 Gy, only about 8% of the initial injury was remembered in young adult guinea pigs. The amount of residual injury was dependent on the initial damage as a proportion of the tolerance dose. The spinal cord shows a greater capacity for long-term recovery than generally appreciated and re-treatment doses clinically prescribed may be lower than necessary. 8 refs., 3 figs., 2 tabs.« less

Influence of ECG measurement accuracy on ECG diagnostic statements.

PubMed

Zywietz, C; Celikag, D; Joseph, G

1996-01-01

Computer analysis of electrocardiograms (ECGs) provides a large amount of ECG measurement data, which may be used for diagnostic classification and storage in ECG databases. Until now, neither error limits for ECG measurements have been specified nor has their influence on diagnostic statements been systematically investigated. An analytical method is presented to estimate the influence of measurement errors on the accuracy of diagnostic ECG statements. Systematic (offset) errors will usually result in an increase of false positive or false negative statements since they cause a shift of the working point on the receiver operating characteristics curve. Measurement error dispersion broadens the distribution function of discriminative measurement parameters and, therefore, usually increases the overlap between discriminative parameters. This results in a flattening of the receiver operating characteristics curve and an increase of false positive and false negative classifications. The method developed has been applied to ECG conduction defect diagnoses by using the proposed International Electrotechnical Commission's interval measurement tolerance limits. These limits appear too large because more than 30% of false positive atrial conduction defect statements and 10-18% of false intraventricular conduction defect statements could be expected due to tolerated measurement errors. To assure long-term usability of ECG measurement databases, it is recommended that systems provide its error tolerance limits obtained on a defined test set.

Roentgen stereophotogrammetric analysis of metal-backed hemispherical cups without attached markers.

PubMed

Valstar, E R; Spoor, C W; Nelissen, R G; Rozing, P M

1997-11-01

A method for the detection of micromotion of a metal-backed hemispherical acetabular cup is presented and tested. Unlike in conventional roentgen stereophotogrammetric analysis, the cup does not have to be marked with tantalum markers; the micromotion is calculated from the contours of the hemispherical part and the base circle of the cup. In this way, two rotations (tilt and anteversion) and the translations along the three cardinal axes are obtained. In a phantom study, the maximum error in the position of the cup's centre was 0.04 mm. The mean error in the orientation of the cup was 0.41 degree, with a 95% confidence interval of 0.28-0.54 degree. The in vivo accuracy was tested by repeated measurement of 21 radiographs from seven patients. The upper bound of the 95% tolerance interval for the translations along the transversal, longitudinal, and sagittal axes was 0.09, 0.07, and 0.34 mm, respectively: for the rotation, this upper bound was 0.39 degree. These results show that the new method, in which the position and orientation of metal-backed hemispherical cup is calculated from its projected contours, is a simple and accurate alternative to attaching markers to the cup.

Inverse axial mounting stiffness design for lithographic projection lenses.

PubMed

Wen-quan, Yuan; Hong-bo, Shang; Wei, Zhang

2014-09-01

In order to balance axial mounting stiffness of lithographic projection lenses and the image quality under dynamic working conditions, an easy inverse axial mounting stiffness design method is developed in this article. Imaging quality deterioration at the wafer under different axial vibration levels is analyzed. The desired image quality can be determined according to practical requirements, and axial vibrational tolerance of each lens is solved with the damped least-squares method. Based on adaptive interval adjustment, a binary search algorithm, and the finite element method, the axial mounting stiffness of each lens can be traveled in a large interval, and converges to a moderate numerical solution which makes the axial vibrational amplitude of the lens converge to its axial vibrational tolerance. Model simulation is carried out to validate the effectiveness of the method.

Recent and Future Enhancements in NDI for Aircraft Structures (Postprint)

DTIC Science & Technology

2015-11-01

found that different capabilities were being used to determine inspection intervals for different aircraft [7]. This led to an internal effort...capability of the NDI technique determines the inspection intervals and the Distribution Statement A. Approved for public release; distribution...damage and that the aircraft structure had to be inspectable . The results of the damage tolerance assessments were incorporated into USAF Technical

Recent and Future Enhancement in NDI for Aircraft Structures (Postprint)

DTIC Science & Technology

2015-11-01

found that different capabilities were being used to determine inspection intervals for different aircraft [7]. This led to an internal effort...capability of the NDI technique determines the inspection intervals and the Distribution Statement A. Approved for public release; distribution...damage and that the aircraft structure had to be inspectable . The results of the damage tolerance assessments were incorporated into USAF Technical

A pilot, open-label, 8-week study evaluating desvenlafaxine for treatment of major depression in methadone-maintained individuals with opioid use disorder.

PubMed

El Hage, Cynthia; Ghabrash, Maykel F; Dubreucq, Simon; Brissette, Suzanne; Lespérance, François; Lespérance, Paul; Ouellet-Plamondon, Clairélaine; Bruneau, Julie; Jutras-Aswad, Didier

2018-05-07

Depression is one of the most prevalent psychiatric disorders among opioid-dependent individuals. Clinical trials testing selective serotonin reuptake inhibitors among depressed patients on methadone maintenance therapy (MMT) failed to show efficacy, whereas those on tricyclic antidepressants produced mixed results with potential for cardiotoxicity. Desvenlafaxine (DESV) is a SNRI with minimal cardiotoxicity and drug interactions. This study sought to assess feasibility and tolerability of using DESV in depressed patients on MMT. A total of 18 depressed individuals on MMT received DESV (50-100 mg/day) for 8 weeks. Participants were assessed for the following: (a) Safety of DESV using Systematic Assessment for Treatment Emergent Events-GI, ECG [corrected Q-T (QTc) interval measurement] and methadone serum levels; (b) depressive symptoms using Montgomery-Äsberg Depression Rating Scale (MADRS); and (c) other outcomes including anxiety, suicidality, craving, substance use, quality of life, and other depression scales. Registration number on ClinicalTrials.gov is NCT02200406. Among participants who completed the study, MADRS scores significantly decreased at week 8 compared with baseline. Responders and remitters on MADRS at week 8 were 61 and 50%, respectively. There was no significant change in [corrected Q-T (QTc) interval measurement] between baseline and week 4. DESV was well tolerated and associated with improvement of depressive symptoms. DESV may be a promising contender to treat depression in individuals on MMT and deserves further exploration in a randomized double-blinded clinical trial.

Contextualizing Parasympathetic Hyperactivity in Functionally Overreached Athletes With Perceptions of Training Tolerance.

PubMed

Bellenger, Clint R; Karavirta, Laura; Thomson, Rebecca L; Robertson, Eileen Y; Davison, Kade; Buckley, Jonathan D

2016-07-01

Heart-rate variability (HRV) as a measure of autonomic function may increase in response to training interventions leading to increases or decreases in performance, making HRV interpretation difficult in isolation. This study aimed to contextualize changes in HRV with subjective measures of training tolerance. Supine and standing measures of vagally mediated HRV (root-mean-square difference of successive normal RR intervals [RMSSD]) and measures of training tolerance (Daily Analysis of Life Demands for Athletes questionnaire, perception of energy levels, fatigue, and muscle soreness) were recorded daily during 1 wk of light training (LT), 2 wk of heavy training (HT), and 10 d of tapering (T) in 15 male runners/ triathletes. HRV and training tolerance were analyzed as rolling 7-d averages at LT, HT, and T. Performance was assessed after LT, HT, and T with a 5-km treadmill time trial (5TTT). Time to complete the 5TTT likely increased after HT (effect size [ES] ± 90% confidence interval = 0.16 ± 0.06) and then almost certainly decreased after T (ES = -0.34 ± 0.08). Training tolerance worsened after HT (ES ≥ 1.30 ± 0.41) and improved after T (ES ≥ 1.27 ± 0.49). Standing RMSSD very likely increased after HT (ES = 0.62 ± 0.26) and likely remained higher than LT at the completion of T (ES = 0.38 ± 0.21). Changes in supine RMSSD were possible or likely trivial. Vagally mediated HRV during standing increased in response to functional overreaching (indicating potential parasympathetic hyperactivity) and also to improvements in performance. Thus, additional measures such as training tolerance are required to interpret changes in vagally mediated HRV.

Lactitol tolerance in healthy Thai adults.

PubMed

Soontornchai, S; Sirichakwal, P; Puwastien, P; Tontisirin, K; Krüger, D; Grossklaus, R

1999-10-01

The hydrogen breath analysis test was performed in healthy Thai adults to determine lactitol tolerance. The study was conducted in 39 individuals (11 males and 28 females) aged 18-41 years. All volunteers agreed to participate in this study after the risks and benefits had been fully explained. Subjects were requested not to consume milk, milk products, or high-vegetable diets for a day and to fast from 10 p.m. of the day preceding the test day. After consumption of the test diet (12 and 20 g of lactose or lactitol, respectively, in 250 mL water), the subjects recorded the severity of symptoms for 24 hours. Breath samples were collected after fasting and after consumption of the test diet at 30 min intervals over the 7-hour study period. Breath samples were analyzed for hydrogen using gas chromatography. After consumption of 12 g lactose, the prevalence of lactose malabsorbers was established. The increment of a peak breath hydrogen level of > or = 20 ppm above the baseline level was used as an indicator of lactose malabsorption. The lactose malabsorbers were further classified as lactose tolerance or lactose intolerance according to the gastrointestinal symptoms observed. All 39 healthy Thai adults could be classified into 3 groups as follows: 9 (23%) lactose absorbers (LA), 15 (38.5%) lactose mal-absorber/tolerance (LMT), and 15 (38.5%) lactose mal-absorber/intolerance (LMI). Using the hydrogen breath test, 67% of the subjects were identified as lactitol intolerance after the consumption of 12 g lactitol. The lactitol intolerance comprised 53.8% of LMI, 34.6% of LMT, and 11.5% of LA. Among all subjects, one third of LA (33%), two thirds of LMT (60%), and 93% of LMI were lactitol intolerant. In addition, gastrointestinal symptoms such as flatulence and abdominal pain were most pronounced in LMI. Diarrhea was also a prominent manifestation after consumption of 12 g lactitol. Therefore, it was finally decided that 20 g lactose or lactitol were not given to LMI because of the risk of gastrointestinal symptoms. After high doses (20 g) of lactose and lactitol consumption, most LMT developed more symptoms than did LA and the main symptom was diarrhea. Consumption of 20 g lactose resulted in fewer symptoms than 20 g lactitol in both LA and LMT. On the basis of the hydrogen breath test, most LA tolerated 12 g lactitol without gastrointestinal symptoms except some flatulence whereas most LMT and LMI did not. Twenty g lactitol was not tolerated by both LA and LMT because there was diarrhea among the subjects, especially in LMT. Although the hydrogen breath analysis test is the best method for identification of lactose malabsorption, it is not the best method to identify lactitol intolerance. A hydrogen concentration of 15 ppm above the baseline level was found to be the best cut-off point to indicate lactitol intolerance although sensitivity was 85% and specificity only 38% in this study. It was further concluded that there is a greater susceptibility to lactitol in human lactose malabsorbers than in lactose absorbers. Our findings might be relevant for the limited use of lactitol in Thailand.

Biotransformation of glyceryl trinitrate occurs concurrently with relaxation of rabbit aorta

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

Brien, J.F.; McLaughlin, B.E.; Breedon, T.H.

1986-05-01

This study was conducted to test the hypothesis that biotransformation of glyceryl trinitrate (GTN) is involved in GTN-induced relaxation of vascular smooth muscle. Isolated rabbit aortic strips (RAS) were contracted submaximally with phenylephrine (PE) and then were incubated with 0.5 microM (/sup 14/C)GTN in a time course study. GTN-induced relaxation (inhibition of PE-induced tone) of RAS was monitored and tissue GTN and glyceryl-1,2- and 1,3-dinitrate (GDN) concentrations were measured by thin-layer chromatography and liquid scintillation spectrometry at 0.5, 1, 2 and 20 min after incubation. Biotransformation of GTN to GDN occurred during GTN-induced relaxation of RAS. The tissue GDN concentrationmore » was dependent on the time duration of incubation with GTN and was related to the magnitude of GTN-induced tissue relaxation. At the 20-min interval, the GDN concentration in the incubation medium indicated appreciable efflux of GDN metabolites from the RAS. In the biotransformation of GTN by RAS, there was about 4-fold preferential formation of 1,2-GDN compared with 1,3-GDN. RAS were made tolerant to GTN in vitro by incubation with 500 microM GTN for 1 hr. After washing, GTN-tolerant and nontolerant (incubation with vehicle for 1 hr) RAS were contracted submaximally with PE, and then were incubated with 0.5 microM (/sup 14/C)GTN for 2 min. GTN-induced relaxation of RAS and tissue GDN concentration were significantly less for GTN-tolerant tissue compared with nontolerant tissue. Tissue GTN concentration was similar for both GTN-tolerant and nontolerant RAS, which indicated that the tissue uptake of GTN was similar and that GTN biotransformation was diminished in tolerant tissue.(ABST« less

Pavlovian control of cross-tolerance between pentobarbital and ethanol.

PubMed

Cappell, H; Roach, C; Poulos, C X

1981-01-01

Tolerance to several effects of a number of drugs has been shown to depend on Pavlovian conditioning processes. Experiment I extended the compensatory conditioning model (Siegel 1975) to tolerance to the hypothermic effect of pentobarbital (30 mg/kg). In Experiment I, rats that acquired hypothermic tolerance in one environment did not display tolerance when tested in an environment not previously associated with drug administration. In Experiment II, rats were made tolerant to the hypothermic effect of pentobarbital (30 mg/kg) and tested for cross-tolerance to ethanol (2.5 g/kg). Cross-tolerance was observed, but it was significantly reduced if the test was in an environment different from the one in which tolerance to pentobarbital was originally acquired. Thus, the compensatory conditioning model accounts for at least part of the tolerance and cross-tolerance to the thermic effects of alcohol and pentobarbital. The physiological processes in the CNS underlying tolerance and cross-tolerance for these drugs, therefore, are controlled by associative processes.

Technical Note: A Feasibility Study of Using the Flat Panel Detector on Linac for the kV X-ray Generator Test.

PubMed

Cai, Bin; Dolly, Steven; Kamal, Gregory; Yaddanapudi, Sridhar; Sun, Baozhou; Goddu, S Murty; Mutic, Sasa; Li, Hua

2018-04-28

To investigate the feasibility of using kV flat panel detector on linac for consistency evaluations of kV X-ray generator performance. An in-house designed aluminum (Al) array phantom with six 9×9 cm 2 square regions having various thickness was proposed and used in this study. Through XML script-driven image acquisition, kV images with various acquisition settings were obtained using the kV flat panel detector. Utilizing pre-established baseline curves, the consistency of X-ray tube output characteristics including tube voltage accuracy, exposure accuracy and exposure linearity were assessed through image quality assessment metrics including ROI mean intensity, ROI standard deviation (SD) and noise power spectrums (NPS). The robustness of this method was tested on two linacs for a three-month period. With the proposed method, tube voltage accuracy can be verified through conscience check with a 2% tolerance and 2 kVp intervals for forty different kVp settings. The exposure accuracy can be tested with a 4% consistency tolerance for three mAs settings over forty kVp settings. The exposure linearity tested with three mAs settings achieved a coefficient of variation (CV) of 0.1. We proposed a novel approach that uses the kV flat panel detector available on linac for X-ray generator test. This approach eliminates the inefficiencies and variability associated with using third party QA detectors while enabling an automated process. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Unrecognized heart failure and chronic obstructive pulmonary disease (COPD) in frail elderly detected through a near-home targeted screening strategy.

PubMed

van Mourik, Yvonne; Bertens, Loes C M; Cramer, Maarten J M; Lammers, Jan-Willem J; Reitsma, Johannes B; Moons, Karel G M; Hoes, Arno W; Rutten, Frans H

2014-01-01

Reduced exercise tolerance and dyspnea are common in older people, and heart failure (HF) and chronic obstructive pulmonary disease (COPD) are the main causes. We want to determine the prevalence of previously unrecognized HF, COPD, and other chronic diseases in frail older people using a near-home targeted screening strategy. Community-dwelling frail persons aged ≥65 years underwent a 2-step screening strategy. First, they received a questionnaire inquiring about dyspnea and exercise tolerance. Those with exercise intolerance and/or dyspnea were invited to visit their primary care physician's office for a screening program, including medical history taking, physical examination, blood tests, electrocardiography, spirometry, and echocardiography. The final diagnosis of every patient was determined by a panel consisting of 3 physicians. Of the 570 elderly who filled out the questionnaire, 395 (69%) had reduced exercise tolerance or dyspnea. Of these, 389 underwent the screening program: 127 (33.5%, 95% confidence interval, 28.9-38.4%) were newly diagnosed with HF (mainly HF with a preserved ejection fraction [23.5%]), and previously unrecognized COPD was detected in 16.8% (95% confidence interval, 13.4-20.9%). In total, 165 patients (43.9%) received a new diagnosis of either HF, COPD, or both. Other new diagnoses (in 32.7% of the screening program patients) included atrial fibrillation (1.8%), valvular disease (21.4%), (persisting) asthma (3.1%), anemia (12.7%), and thyroid disease (0.6%). No clear explanation for the complaints of 47 patients (12.2%) was found using our strategy. Unrecognized chronic diseases might be detected in community-dwelling frail elderly using a near-home screening strategy that is simple to implement. It remains to be proven, however, whether optimizing treatment of the newly detected diagnoses in this fragile population with multimorbidities and polypharmacy improves quality of life and reduces morbidity and mortality. © Copyright 2014 by the American Board of Family Medicine.

Emergency department treatment of viral gastritis using intravenous ondansetron or dexamethasone in children.

PubMed

Stork, Christine M; Brown, Kathleen M; Reilly, Tracey H; Secreti, LaLaina; Brown, Lawrence H

2006-10-01

To compare the efficacy of intravenous ondansetron or dexamethasone compared with intravenous fluid therapy alone in children presenting to the emergency department with refractory vomiting from viral gastritis who had failed attempts at oral hydration. This double-blind, randomized, controlled trial was performed in a tertiary care pediatric emergency department. Children aged 6 months to 12 years presenting with more than three episodes of vomiting in the past 24 hours, mild/moderate dehydration, and failed oral hydration were included. Patients with other medical causes were excluded. Subjects were randomized to dexamethasone 1 mg/kg (15 mg maximum), ondansetron 0.15 mg/kg, or placebo (normal saline [NS], 10 mL). All subjects also received intravenous NS at 10-20 mL/kg/hr. Oral fluid tolerance was evaluated at two and four hours. Those not tolerating oral fluids at four hours were admitted. Discharged patients were evaluated at 24 and 72 hours for vomiting and repeat health care visits. The primary study outcome was hospitalization rates between the groups. Data were analyzed using chi-square test, Kruskal-Wallis test, Mantel-Haenszel test, and analysis of variance, with p < 0.05 considered significant. A total of 166 subjects were enrolled; data for analysis were available for 44 NS-treated patients, 46 ondansetron-treated patients, and 47 dexamethasone-treated patients. Hospital admission occurred in nine patients (20.5%) receiving placebo (NS alone), two patients (4.4%) receiving ondansetron, and seven patients (14.9%) receiving dexamethasone, with ondansetron significantly different from placebo (p = 0.02). Similarly, at two hours, more ondansetron-treated patients (39 [86.6%]) tolerated oral hydration than NS-treated patients (29 [67.4%]; relative risk, 1.28; 95% confidence interval = 1.02 to 1.68). There were no differences in number of mean episodes of vomiting or repeat visits to health care at 24 and 72 hours in the ondansetron, dexamethasone, or NS groups. In children with dehydration secondary to vomiting from acute viral gastritis, ondansetron with intravenous rehydration improves tolerance of oral fluids after two hours and reduces the hospital admission rate when compared with intravenous rehydration with or without dexamethasone.

Glucose tolerance status of Asian Indian women with gestational diabetes at 6weeks to 1year postpartum (WINGS-7).

PubMed

Bhavadharini, Balaji; Anjana, Ranjit Mohan; Mahalakshmi, Manni Mohanraj; Maheswari, Kumar; Kayal, Arivudainambi; Unnikrishnan, Ranjit; Ranjani, Harish; Ninov, Lyudmil; Pastakia, Sonak D; Usha, Sriram; Malanda, Belma; Belton, Anne; Uma, Ram; Mohan, Viswanathan

2016-07-01

To determine postpartum glucose tolerance status among women with gestational diabetes mellitus (GDM) recruited under the Women In India with GDM Strategy (WINGS) Model of Care (MOC). Through the WINGS MOC programme, 212 women with GDM were followed till delivery between November 2013 and August 2015. All women were advised to return for a postpartum oral glucose tolerance test (OGTT) 6-12weeks after delivery. A multivariate logistic regression (MLR) model was developed to identify the risk factors for postpartum dysglycemia which was defined as presence of diabetes (DM) or prediabetes. 203/212(95.8%) women completed their postpartum OGTT. Of the 161 women (79.3%) who came back for the test between 6 and 12weeks, 2(1.2%) developed DM, 5(3.1%), isolated IFG, 13(8.1%), isolated IGT and 5(3.1%) combined IFG/IGT [dysglycemia 25(15.5%)]. 136 women (84.5%) reverted to normal glucose tolerance (NGT). Of the 42 women who came back between 12weeks and a year, 5(11.9%) developed DM, 10(23.8%), isolated IFG and 1(2.4%) combined IFG/IGT [dysglycemia 16(38.1%)]. 26/42 women (61.9%) reverted to NGT. Thus overall dysglycemia occurred in 41/203 women (20.2%). MLR showed that BMI ⩾25kg/m(2) was significantly associated with postpartum dysglycemia (odds ratio: 4.47; 95% confidence interval: 1.8-11.2, p=0.001). Among Asian Indian women with GDM, over 20% develop dysglycemia within one year postpartum, and BMI ⩾25kg/m(2) increased this risk four-fold. Early postpartum screening can identify high risk women and help plan strategies for prevention of type 2 diabetes in the future. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

Itopride for gastric volume, gastric emptying and drinking capacity in functional dyspepsia

PubMed Central

Abid, Shahab; Jafri, Wasim; Zaman, Maseeh Uz; Bilal, Rakhshanda; Awan, Safia; Abbas, Aamir

2017-01-01

AIM To study the effect of itopride on gastric accommodation, gastric emptying and drinking capacity in functional dyspepsia (FD). METHODS Randomized controlled trial was conducted to check the effect of itopride on gastric accommodation, gastric emptying, capacity of tolerating nutrient liquid and symptoms of FD. We recruited a total of 31 patients having FD on the basis of ROME III criteria. After randomization, itopride was received by 15 patients while 16 patients received placebo. Gastric accommodation was determined using Gastric Scintigraphy. 13C labeled octanoic breadth test was performed to assess gastric emptying. Capacity of tolerating nutrient liquid drink was checked using satiety drinking capacity test. The intervention group comprised of 150 mg itopride. Patients in both arms were followed for 4 wk. RESULTS Mean age of the recruited participant 33 years (SD = 7.6) and most of the recruited individuals, i.e., 21 (67.7%) were males. We found that there was no effect of itopride on gastric accommodation as measured at different in volumes in the itopride and control group with the empty stomach (P = 0.14), at 20 min (P = 0.38), 30 min (P = 0.30), 40 min (P = 0.43), 50 min (P = 0.50), 60 min (P = 0.81), 90 min (P = 0.25) and 120 min (P = 0.67). Gastric emptying done on a sub sample (n = 11) showed no significant difference (P = 0.58) between itopride and placebo group. There was no significant improvement in the capacity to tolerate liquid in the itopride group as compared to placebo (P = 0.51). Similarly there was no significant improvement of symptoms as assessed through a composite symptom score (P = 0.74). The change in QT interval in itopride group was not significantly different from placebo (0.10). CONCLUSION Our study found no effect of itopride on gastric accommodation, gastric emptying and maximum tolerated volume in patients with FD. PMID:28217377

Itopride for gastric volume, gastric emptying and drinking capacity in functional dyspepsia.

PubMed

Abid, Shahab; Jafri, Wasim; Zaman, Maseeh Uz; Bilal, Rakhshanda; Awan, Safia; Abbas, Aamir

2017-02-06

To study the effect of itopride on gastric accommodation, gastric emptying and drinking capacity in functional dyspepsia (FD). Randomized controlled trial was conducted to check the effect of itopride on gastric accommodation, gastric emptying, capacity of tolerating nutrient liquid and symptoms of FD. We recruited a total of 31 patients having FD on the basis of ROME III criteria. After randomization, itopride was received by 15 patients while 16 patients received placebo. Gastric accommodation was determined using Gastric Scintigraphy. 13 C labeled octanoic breadth test was performed to assess gastric emptying. Capacity of tolerating nutrient liquid drink was checked using satiety drinking capacity test. The intervention group comprised of 150 mg itopride. Patients in both arms were followed for 4 wk. Mean age of the recruited participant 33 years (SD = 7.6) and most of the recruited individuals, i.e ., 21 (67.7%) were males. We found that there was no effect of itopride on gastric accommodation as measured at different in volumes in the itopride and control group with the empty stomach ( P = 0.14), at 20 min ( P = 0.38), 30 min ( P = 0.30), 40 min ( P = 0.43), 50 min ( P = 0.50), 60 min ( P = 0.81), 90 min ( P = 0.25) and 120 min ( P = 0.67). Gastric emptying done on a sub sample ( n = 11) showed no significant difference ( P = 0.58) between itopride and placebo group. There was no significant improvement in the capacity to tolerate liquid in the itopride group as compared to placebo ( P = 0.51). Similarly there was no significant improvement of symptoms as assessed through a composite symptom score ( P = 0.74). The change in QT interval in itopride group was not significantly different from placebo (0.10). Our study found no effect of itopride on gastric accommodation, gastric emptying and maximum tolerated volume in patients with FD.

Evaluation of the Safety, Tolerability, and Pharmacokinetics of Gammaplex® 10% Versus Gammaplex® 5% in Subjects with Primary Immunodeficiency.

PubMed

Wasserman, Richard L; Melamed, Isaac R; Stein, Mark R; Jolles, Stephen; Norton, Miranda; Moy, James N

2017-04-01

This phase 3, multicenter, open-label, randomized, two-period, crossover bioequivalence trial evaluated the safety, tolerability, and pharmacokinetics of intravenous immunoglobulins (IVIGs) Gammaplex 5% and Gammaplex 10% in 33 adults and 15 children with primary immunodeficiency diseases (PIDs). Eligible adults received five Gammaplex 5% infusions followed by five Gammaplex 10% infusions, or vice versa, stratified by a 21- or 28-day dosing regimen. Pediatric subjects received five Gammaplex 10% infusions only. The primary objective, to demonstrate the bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval, was met based on the Gammaplex 10%/Gammaplex 5% ratio of area under the concentration versus time curve (AUC 0-28 ) values. Throughout the study, total immunoglobulin G trough levels were well maintained, with total values generally ≥600 mg/dL (minimum level for study inclusion). At the dosing schedules and infusion rates used in this study, safety and tolerability were comparable and acceptable in adult and pediatric PID subjects treated with Gammaplex 10% and 5%. In this study, the first direct comparison of 5% IVIG and 10% IVIG products in PID subjects, the pharmacokinetic analysis demonstrated bioequivalence of Gammaplex 10% and Gammaplex 5% at the 28-day dosing interval. The Gammaplex 10% formulation was safe and well tolerated in pediatric and adult PID subjects. Based on the results from this bridging study in PID subjects, Gammaplex 10% could be expected to have a therapeutic effect similar to the licensed Gammaplex 5%, which has demonstrated efficacy and tolerability in patients with PID and idiopathic thrombocytopenic purpura.

Measuring the RC time constant with Arduino

NASA Astrophysics Data System (ADS)

Pereira, N. S. A.

2016-11-01

In this work we use the Arduino UNO R3 open source hardware platform to assemble an experimental apparatus for the measurement of the time constant of an RC circuit. With adequate programming, the Arduino is used as a signal generator, a data acquisition system and a basic signal visualisation tool. Theoretical calculations are compared with direct observations from an analogue oscilloscope. Data processing and curve fitting is performed on a spreadsheet. The results obtained for the six RC test circuits are within the expected interval of values defined by the tolerance of the components. The hardware and software prove to be adequate to the proposed measurements and therefore adaptable to a laboratorial teaching and learning context.

Six-minute-walk test in idiopathic pulmonary fibrosis: test validation and minimal clinically important difference.

PubMed

du Bois, Roland M; Weycker, Derek; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; Kartashov, Alex; Lancaster, Lisa; Noble, Paul W; Sahn, Steven A; Szwarcberg, Javier; Thomeer, Michiel; Valeyre, Dominique; King, Talmadge E

2011-05-01

The 6-minute-walk test (6MWT) is a practical and clinically meaningful measure of exercise tolerance with favorable performance characteristics in various cardiac and pulmonary diseases. Performance characteristics in patients with idiopathic pulmonary fibrosis (IPF) have not been systematically evaluated. To assess the reliability, validity, and responsiveness of the 6MWT and estimate the minimal clinically important difference (MCID) in patients with IPF. The study population included all subjects completing a 6MWT in a clinical trial evaluating interferon gamma-1b (n = 822). Six-minute walk distance (6MWD) and other parameters were measured at baseline and at 24-week intervals using a standardized protocol. Parametric and distribution-independent correlation coefficients were used to assess the strength of the relationships between 6MWD and measures of pulmonary function, dyspnea, and health-related quality of life. Both distribution-based and anchor-based methods were used to estimate the MCID. Comparison of two proximal measures of 6MWD (mean interval, 24 d) demonstrated good reliability (coefficient = 0.83; P < 0.001). 6MWD was weakly correlated with measures of physiologic function and health-related quality of life; however, values were consistently and significantly lower for patients with the poorest functional status, suggesting good construct validity. Importantly, change in 6MWD was highly predictive of mortality; a 24-week decline of greater than 50 m was associated with a fourfold increase in risk of death at 1 year (hazard ratio, 4.27; 95% confidence interval, 2.57- 7.10; P < 0.001). The estimated MCID was 24-45 m. The 6MWT is a reliable, valid, and responsive measure of disease status and a valid endpoint for clinical trials in IPF.

Floating-point geometry: toward guaranteed geometric computations with approximate arithmetics

NASA Astrophysics Data System (ADS)

Bajard, Jean-Claude; Langlois, Philippe; Michelucci, Dominique; Morin, Géraldine; Revol, Nathalie

2008-08-01

Geometric computations can fail because of inconsistencies due to floating-point inaccuracy. For instance, the computed intersection point between two curves does not lie on the curves: it is unavoidable when the intersection point coordinates are non rational, and thus not representable using floating-point arithmetic. A popular heuristic approach tests equalities and nullities up to a tolerance ɛ. But transitivity of equality is lost: we can have A approx B and B approx C, but A not approx C (where A approx B means ||A - B|| < ɛ for A,B two floating-point values). Interval arithmetic is another, self-validated, alternative; the difficulty is to limit the swell of the width of intervals with computations. Unfortunately interval arithmetic cannot decide equality nor nullity, even in cases where it is decidable by other means. A new approach, developed in this paper, consists in modifying the geometric problems and algorithms, to account for the undecidability of the equality test and unavoidable inaccuracy. In particular, all curves come with a non-zero thickness, so two curves (generically) cut in a region with non-zero area, an inner and outer representation of which is computable. This last approach no more assumes that an equality or nullity test is available. The question which arises is: which geometric problems can still be solved with this last approach, and which cannot? This paper begins with the description of some cases where every known arithmetic fails in practice. Then, for each arithmetic, some properties of the problems they can solve are given. We end this work by proposing the bases of a new approach which aims to fulfill the geometric computations requirements.

The Role of Heat Tolerance Testing in Recovery and Return to Duty

DTIC Science & Technology

2008-10-01

CV diseases Hyperthyroidism Pheochromocytoma Infectious diseases Diabetes mellitus Psychiatric illness Parkinsonism Congenital abnormalities: CF...environments. To assess the heat tolerance status of prior heat stroke patient. Heat tolerance test (HTT) “HTT was effective in evaluating the heat tolerance

Evaluation of commercial ADC radiation tolerance for accelerator experiments

DOE PAGES

Chen, K.; Chen, H.; Kierstead, J.; ...

2015-08-17

Electronic components used in high energy physics experiments are subjected to a radiation background composed of high energy hadrons, mesons and photons. These particles can induce permanent and transient effects that affect the normal device operation. Ionizing dose and displacement damage can cause chronic damage which disable the device permanently. Transient effects or single event effects are in general recoverable with time intervals that depend on the nature of the failure. The magnitude of these effects is technology dependent with feature size being one of the key parameters. Analog to digital converters are components that are frequently used in detectormore » front end electronics, generally placed as close as possible to the sensing elements to maximize signal fidelity. We report on radiation effects tests conducted on 17 commercially available analog to digital converters and extensive single event effect measurements on specific twelve and fourteen bit ADCs that presented high tolerance to ionizing dose. We discuss mitigation strategies for single event effects (SEE) for their use in the large hadron collider environment.« less

Fixed-distance walk tests at comfortable and fast speed: Potential tools for the functional assessment of coronary patients?

PubMed

Morard, Marie-Doriane; Besson, Delphine; Laroche, Davy; Naaïm, Alexandre; Gremeaux, Vincent; Casillas, Jean-Marie

2017-01-01

There is ambiguity concerning the walk tests available for functional assessment of coronary patients, particularly for the walking speed. This study explores the psychometric properties of two walking tests, based on fixed-distance tests, at comfortable and fast velocity, in stabilized patients at the end of a cardiac rehabilitation program. At a three-day interval 58 coronary patients (mean age of 64.85±6.03 years, 50 men) performed three walk tests, the first two at a comfortable speed in a random order (6-minute walk test - 6MWT - and 400-metre comfortable walk test - 400mCWT) and the third at a brisk speed (200-metre fast walk test - 200mFWT). A modified Bruce treadmill test was associated at the end of the second phase. Monitored main parameters were: heart rate, walking velocity, VO 2 . Tolerance to the 3 tests was satisfactory. The reliability of the main parameters was good (intraclass correlation coefficient>0.8). The VO 2 concerning 6MWT and 400mCWT were not significantly different (P=0.33) and were lower to the first ventilatory threshold determined by the stress test (P<0.001): 16.2±3.0 vs. 16.5±2.6 vs. 20.7±5.1mL·min -1 ·kg -1 respectively. The VO 2 of the 200mFWT (20.2±3.7) was not different from the first ventilatory threshold. 400mCWT and 200mFWT are feasible, well-tolerated and reliable. They explore two levels of effort intensity (lower and not different to the first ventilatory threshold respectively). 400mCWT is a possible alternative to 6MWT. Associated with 200mFWT it should allow a better measurement of physical capacities and better customization of exercise training. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Association of GPs’ risk attitudes, level of empathy, and burnout status with PSA testing in primary care

PubMed Central

Pedersen, Anette F; Carlsen, Anders H; Vedsted, Peter

2015-01-01

Background Rates of prostate specific antigen (PSA) test ordering vary among GPs. Aim To examine whether GPs’ risk attitude, level of empathy, and burnout status are associated with PSA testing. Design and setting Register and questionnaire study including 129 solo GPs (active in the Central Denmark Region) and 76 672 of their adult male patients with no history of or current prostate cancer diagnosis. Method PSA tests from 2012 were retrieved from a register and classified as incident (that is, the first PSA test within 24 months), repeated normal, or repeated raised tests. This was merged with information on GPs’ risk attitudes, empathy, and burnout status from a 2012 survey. Results Patients registered with a GP with a high score on anxiety caused by uncertainty (odds ratio [OR] 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.025) or concern about bad outcomes (OR 1.04; 95% CI = 1.00 to 1.08, P = 0.034) were more likely to have an incident PSA test, whereas those registered with a GP with increased tolerance for ambiguity were less likely (OR 0.98, 95% CI = 0.96 to 1.00, P = 0.025). Patients registered with a GP reporting high tolerance for ambiguity (OR 0.96, 95% CI = 0.94 to 0.99, P = 0.009) or high propensity to risk-taking (OR 0.97, 95% CI = 0.93 to 1.00, P = 0.047) were less likely to have a repeated normal PSA test. Conclusion Various aspects of GPs’ risk-taking attitudes were associated with patients’ probability of having an incident and a repeated normal PSA test. The probability of having a repeated raised PSA test was not influenced by any of the psychological factors. Burnout and empathy were not associated with PSA testing. PMID:26541183

Susceptibility of Culicidae Mosquitoes to Some Insecticides Recommended by WHO in a Malaria Endemic Area of Southeastern Iran

PubMed Central

Fathian, Mousa; Vatandoost, Hassan; Moosa-Kazemi, Seyed Hassan; Raeisi, Ahmad; Yaghoobi-Ershadi, Mohammad Reza; Oshaghi, Mohammad Ali; Sedaghat, Mohammad Mehdi

2015-01-01

Background: According to the national strategy plan on monitoring of insecticides resistance, this study was carried out to determine the base line susceptibility of the Culicidae mosquitoes to the WHO-recommended insecticides in an endemic focus of malaria in southeastern Iran. Methods: Larval collection was carried out by dipping method and adult collection occurred by suction tube from January to December 2010. The susceptibility test was assessed to DDT 4 %, malathion 5 %, propoxur 0.1 %, deltamethrin 0.05 %, lambda-cyhalothrin 0.05 %, and cyfluthrin 0.15 % at different interval times (discriminative dose) followed by 24 h recovery period. The LT50 and LT90 values were calculated for plotting the regression line using Microsoft office Excel software ver. 2007. Results: Anopheles stephensi was quite resistant to DDT and showed susceptible or tolerant to other insecticides. The LT50 and LT90 values to DDT in this species were 29.07, and 98.26 minutes, respectively. Anopheles culicifacies and Anopheles dthali were found susceptible or tolerant to insecticides. Culex pipiens was found resistance to DDT, propoxur, lambda-cyhalothrin and cyfluthrin whereas observed susceptible to malathion and tolerant to deltamethrin. Ochlerotatus caspius sl. was resistant to DDT, whereas found susceptible to other insecticides. Culisita longiareolata was susceptible to deltamethrin, whereas tolerant to other insecticides. The LT50 and LT90 values of Cs. longiareolata to DDT were 17.82, and 51.26 minutes. Conclusion: We suggested the same study in different parts of the country for monitoring and evaluation of control measures. PMID:26114141

Glucose in vaginal secretions before and after oral glucose tolerance testing in women with and without recurrent vulvovaginal candidiasis.

PubMed

Ehrström, Sophia; Yu, Anna; Rylander, Eva

2006-12-01

To measure the change of glucose in vaginal secretions during glucose tolerance testing in women with recurrent vulvovaginal candidiasis and in healthy control subjects. Thirty-eight women with recurrent vulvovaginal candidiasis and 45 healthy, age-matched controls completed a health questionnaire regarding general and gynecologic health and food and alcohol habits. They all underwent an oral glucose tolerance test and a vaginal examination. Vaginal secretion was collected from the proximal part of the vagina. Glucose in plasma and in vaginal secretions were measured at fasting and after 2 hours and analyzed with the hexokinase method. A sample size analysis showed that the number of subjects included in the study was sufficient for a beta value of 0.80, at the significance level of alpha=.05, at a difference in glucose in vaginal secretions of 30% after oral glucose tolerance test. In healthy women, the median level of glucose in vaginal secretions was 5.2 mM before and 3.7 mM after oral glucose tolerance test, and plasma glucose was 5.0 mM before and 5.8 mM after oral glucose tolerance test. No significant difference was seen regarding change of glucose level in vaginal secretions and plasma glucose after testing, compared with before oral glucose tolerance testing. There were no differences between women with recurrent vulvovaginal candidiasis and control subjects regarding change in glucose level in vaginal secretions or in plasma during oral glucose tolerance test. II-2.

Fuel containment and damage tolerance for large composite primary aircraft structures. Phase 1: Testing

NASA Technical Reports Server (NTRS)

Sandifer, J. P.

1983-01-01

Technical problems associated with fuel containment and damage tolerance of composite material wings for transport aircraft were identified. The major tasks are the following: (1) the preliminary design of damage tolerant wing surface using composite materials; (2) the evaluation of fuel sealing and lightning protection methods for a composite material wing; and (3) an experimental investigation of the damage tolerant characteristics of toughened resin graphite/epoxy materials. The test results, the test techniques, and the test data are presented.

Hypoglycemic and hypolipidemic activities of crude seeds of Centratherum anthelminticum in healthy volunteers and type 2 diabetic patients.

PubMed

Mudassir, Hina Akram; Qureshi, Shamim Akhter; Azmi, Muhammad Bilal; Ahsan, Muhammad; Kamran, Musab; Jafar, Sakina

2018-05-01

This study first time reports the hypoglycaemic activity of crude seeds powder (CSP) of Centratherum anthelminticum in healthy and type 2 diabetic volunteers. In addition, hypolipidemic effect of same CSP was also determined in healthy volunteers. Healthy individuals were divided into control and two test groups T1 and T2 treated with 200 & 400mg of CSP. Similarly, type 2 diabetic patients were also divided into positive control (PC) treated with metformin 600mg and two test groups DT1 (CSP 400mg + metformin 600mg) & DT2 (CSP 400mg). Each group has 6 individuals and each treatment was done orally. CSP 400mg was found more hypoglycaemic on all time intervals from 30 to 120min when oral glucose tolerance test was conducted in healthy volunteers. Both test quantities of CSP 200 & 400 mg were found successful in same healthy persons in decreasing the levels of triglycerides & total cholesterol (p<0.05), low & very low density lipoprotein cholesterols (p<0.01) and keeping the level of high density lipoprotein cholesterol as same as it was observed in control group. Similarly, CSP 400mg along with metformin and alone was also found helpful in lowering the fasting blood glucose levels in type 2 diabetic patients (DT1 & DT2) -24.99% and -20.62% respectively as compared to diabetic group only treated with metformin (PC), (p<0.01). Therefore, CSP of C antheminticum proves effective hypoglycaemic and hypolipidemic agent by possibly inducing glucose tolerance in healthy individuals and type 2 diabetic patients.

Glucose concentration in the blood of intact and alloxan-treated mice after pretreatment with commercial preparations of Stevia rebaudiana (Bertoni).

PubMed

Raskovic, Aleksandar; Gavrilovic, Maja; Jakovljevic, Vida; Sabo, Jan

2004-01-01

The study was concerned with the effect of mice pretreatment with two commercial products of Stevia rebaudiana Bertoni on the blood glucose concentration. One group of mice was pretreated four days with 200 mg/kg of Stevita (Stevita Co, INC, Arlington Texas) (stevia) and the other with 20 mg/kg of Clear Steviosides liquid (Stevita Co, INC, Herbal supplement, Brazil) (stevioside), whereas the animals of control group received at the same time physiological solution. Blood glucose concentration was measured before pretreatment and four days after that. The changes in glucose level were provoked by glucose-tolerance test (500 mg/kg, p.o.) and subcutaneous injection of adrenaline (0.2 mg/kg). The same procedure of measuring blood glucose was applied on the mice with alloxan-induced diabetes mellitus (two doses of 100 mg/kg with a 24-hour interval). Blood glucose levels in mice pretreated with stevia and stevioside were lower compared with control (7.82:6.82:8.01). Also, a smaller increase in this parameter compared to control was registered with pretreated mice in the glucose-tolerance test, pretreatment with stevioside being again more effective (8.68:6.36:5.82). Pretreatment with stevioside caused no significant increase in blood glucose concentration after administering adrenaline, which was not the case with the animals pretreated with stevia and control. Pretreatment with stevia, and to a greater extent with stevioside, protected test animals from the toxic action of alloxan compared with controls.

Risk management for moisture related effects in dry manufacturing processes: a statistical approach.

PubMed

Quiroz, Jorge; Strong, John; Zhang, Lanju

2016-03-01

A risk- and science-based approach to control the quality in pharmaceutical manufacturing includes a full understanding of how product attributes and process parameters relate to product performance through a proactive approach in formulation and process development. For dry manufacturing, where moisture content is not directly manipulated within the process, the variability in moisture of the incoming raw materials can impact both the processability and drug product quality attributes. A statistical approach is developed using individual raw material historical lots as a basis for the calculation of tolerance intervals for drug product moisture content so that risks associated with excursions in moisture content can be mitigated. The proposed method is based on a model-independent approach that uses available data to estimate parameters of interest that describe the population of blend moisture content values and which do not require knowledge of the individual blend moisture content values. Another advantage of the proposed tolerance intervals is that, it does not require the use of tabulated values for tolerance factors. This facilitates the implementation on any spreadsheet program like Microsoft Excel. A computational example is used to demonstrate the proposed method.

In-feed use of heavy metal micronutrients in U.S. swine production systems and its role in persistence of multidrug-resistant salmonellae.

PubMed

Medardus, Julius J; Molla, Bayleyegn Z; Nicol, Matthew; Morrow, W Morgan; Rajala-Schultz, Paivi J; Kazwala, Rudovick; Gebreyes, Wondwossen A

2014-04-01

The study aimed to characterize the role of heavy metal micronutrients in swine feed in emergence of heavy-metal-tolerant and multidrug-resistant Salmonella organisms. We conducted a longitudinal study in 36 swine barns over a 2-year period. The feed and fecal levels of Cu(2+) and Zn(2+) were measured. Salmonella was isolated at early and late finishing. MICs of copper sulfate and zinc chloride were measured using agar dilution. Antimicrobial susceptibility was tested using the Kirby-Bauer method, and 283 isolates were serotyped. We amplified pcoA and czcD genes that encode Cu(2+) and Zn(2+) tolerance, respectively. Of the 283 isolates, 113 (48%) showed Cu(2+) tolerance at 24 mM and 164 (58%) showed Zn(2+) tolerance at 8 mM. In multivariate analysis, serotype and source of isolates were significantly associated with Cu(2+) tolerance (P < 0.001). Fecal isolates were more likely to be Cu(2+) tolerant than those of feed origin (odds ratio [OR], 27.0; 95% confidence interval [CI], 2.8 to 250; P = 0.0042) or environmental origin (OR, 5.8), implying the significance of gastrointestinal selective pressure. Salmonella enterica serotypes Typhimurium and Heidelberg, highly significant for public health, had higher odds of having >20 mM MICs of Cu(2+) than did "other" serotypes. More than 60% of Salmonella isolates with resistance type (R-type) AmStTeKm (32 of 53) carried pcoA; only 5% with R-type AmClStSuTe carried this gene. czcD gene carriage was significantly associated with a higher Zn(2+) MIC (P < 0.05). The odds of having a high Zn(2+) MIC (≥8 mM) were 14.66 times higher in isolates with R-type AmClStSuTe than in those with R-type AmStTeKm (P < 0.05). The findings demonstrate strong association between heavy metal tolerance and antimicrobial resistance, particularly among Salmonella serotypes important in public health.

In-Feed Use of Heavy Metal Micronutrients in U.S. Swine Production Systems and Its Role in Persistence of Multidrug-Resistant Salmonellae

PubMed Central

Medardus, Julius J.; Molla, Bayleyegn Z.; Nicol, Matthew; Morrow, W. Morgan; Rajala-Schultz, Paivi J.; Kazwala, Rudovick

2014-01-01

The study aimed to characterize the role of heavy metal micronutrients in swine feed in emergence of heavy-metal-tolerant and multidrug-resistant Salmonella organisms. We conducted a longitudinal study in 36 swine barns over a 2-year period. The feed and fecal levels of Cu2+ and Zn2+ were measured. Salmonella was isolated at early and late finishing. MICs of copper sulfate and zinc chloride were measured using agar dilution. Antimicrobial susceptibility was tested using the Kirby-Bauer method, and 283 isolates were serotyped. We amplified pcoA and czcD genes that encode Cu2+ and Zn2+ tolerance, respectively. Of the 283 isolates, 113 (48%) showed Cu2+ tolerance at 24 mM and 164 (58%) showed Zn2+ tolerance at 8 mM. In multivariate analysis, serotype and source of isolates were significantly associated with Cu2+ tolerance (P < 0.001). Fecal isolates were more likely to be Cu2+ tolerant than those of feed origin (odds ratio [OR], 27.0; 95% confidence interval [CI], 2.8 to 250; P = 0.0042) or environmental origin (OR, 5.8), implying the significance of gastrointestinal selective pressure. Salmonella enterica serotypes Typhimurium and Heidelberg, highly significant for public health, had higher odds of having >20 mM MICs of Cu2+ than did “other” serotypes. More than 60% of Salmonella isolates with resistance type (R-type) AmStTeKm (32 of 53) carried pcoA; only 5% with R-type AmClStSuTe carried this gene. czcD gene carriage was significantly associated with a higher Zn2+ MIC (P < 0.05). The odds of having a high Zn2+ MIC (≥8 mM) were 14.66 times higher in isolates with R-type AmClStSuTe than in those with R-type AmStTeKm (P < 0.05). The findings demonstrate strong association between heavy metal tolerance and antimicrobial resistance, particularly among Salmonella serotypes important in public health. PMID:24487542

The effects of free-living interval-walking training on glycemic control, body composition, and physical fitness in type 2 diabetic patients: a randomized, controlled trial.

PubMed

Karstoft, Kristian; Winding, Kamilla; Knudsen, Sine H; Nielsen, Jens S; Thomsen, Carsten; Pedersen, Bente K; Solomon, Thomas P J

2013-02-01

To evaluate the feasibility of free-living walking training in type 2 diabetic patients and to investigate the effects of interval-walking training versus continuous-walking training upon physical fitness, body composition, and glycemic control. Subjects with type 2 diabetes were randomized to a control (n = 8), continuous-walking (n = 12), or interval-walking group (n = 12). Training groups were prescribed five sessions per week (60 min/session) and were controlled with an accelerometer and a heart-rate monitor. Continuous walkers performed all training at moderate intensity, whereas interval walkers alternated 3-min repetitions at low and high intensity. Before and after the 4-month intervention, the following variables were measured: VO(2)max, body composition, and glycemic control (fasting glucose, HbA(1c), oral glucose tolerance test, and continuous glucose monitoring [CGM]). Training adherence was high (89 ± 4%), and training energy expenditure and mean intensity were comparable. VO(2)max increased 16.1 ± 3.7% in the interval-walking group (P < 0.05), whereas no changes were observed in the continuous-walking or control group. Body mass and adiposity (fat mass and visceral fat) decreased in the interval-walking group only (P < 0.05). Glycemic control (elevated mean CGM glucose levels and increased fasting insulin) worsened in the control group (P < 0.05), whereas mean (P = 0.05) and maximum (P < 0.05) CGM glucose levels decreased in the interval-walking group. The continuous walkers showed no changes in glycemic control. Free-living walking training is feasible in type 2 diabetic patients. Continuous walking offsets the deterioration in glycemia seen in the control group, and interval walking is superior to energy expenditure-matched continuous walking for improving physical fitness, body composition, and glycemic control.

High-intensity interval training: Modulating interval duration in overweight/obese men.

PubMed

Smith-Ryan, Abbie E; Melvin, Malia N; Wingfield, Hailee L

2015-05-01

High-intensity interval training (HIIT) is a time-efficient strategy shown to induce various cardiovascular and metabolic adaptations. Little is known about the optimal tolerable combination of intensity and volume necessary for adaptations, especially in clinical populations. In a randomized controlled pilot design, we evaluated the effects of two types of interval training protocols, varying in intensity and interval duration, on clinical outcomes in overweight/obese men. Twenty-five men [body mass index (BMI) > 25 kg · m(2)] completed baseline body composition measures: fat mass (FM), lean mass (LM) and percent body fat (%BF) and fasting blood glucose, lipids and insulin (IN). A graded exercise cycling test was completed for peak oxygen consumption (VO2peak) and power output (PO). Participants were randomly assigned to high-intensity short interval (1MIN-HIIT), high-intensity interval (2MIN-HIIT) or control groups. 1MIN-HIIT and 2MIN-HIIT completed 3 weeks of cycling interval training, 3 days/week, consisting of either 10 × 1 min bouts at 90% PO with 1 min rests (1MIN-HIIT) or 5 × 2 min bouts with 1 min rests at undulating intensities (80%-100%) (2MIN-HIIT). There were no significant training effects on FM (Δ1.06 ± 1.25 kg) or %BF (Δ1.13% ± 1.88%), compared to CON. Increases in LM were not significant but increased by 1.7 kg and 2.1 kg for 1MIN and 2MIN-HIIT groups, respectively. Increases in VO2peak were also not significant for 1MIN (3.4 ml·kg(-1) · min(-1)) or 2MIN groups (2.7 ml · kg(-1) · min(-1)). IN sensitivity (HOMA-IR) improved for both training groups (Δ-2.78 ± 3.48 units; p < 0.05) compared to CON. HIIT may be an effective short-term strategy to improve cardiorespiratory fitness and IN sensitivity in overweight males.

High-intensity interval training: Modulating interval duration in overweight/obese men

PubMed Central

Smith-Ryan, Abbie E.; Melvin, Malia N.; Wingfield, Hailee L.

2015-01-01

Introduction High-intensity interval training (HIIT) is a time-efficient strategy shown to induce various cardiovascular and metabolic adaptations. Little is known about the optimal tolerable combination of intensity and volume necessary for adaptations, especially in clinical populations. Objectives In a randomized controlled pilot design, we evaluated the effects of two types of interval training protocols, varying in intensity and interval duration, on clinical outcomes in overweight/obese men. Methods Twenty-five men [body mass index (BMI) > 25 kg·m2] completed baseline body composition measures: fat mass (FM), lean mass (LM) and percent body fat (%BF) and fasting blood glucose, lipids and insulin (IN). A graded exercise cycling test was completed for peak oxygen consumption (VO2peak) and power output (PO). Participants were randomly assigned to high-intensity short interval (1MIN-HIIT), high-intensity interval (2MIN-HIIT) or control groups. 1MIN-HIIT and 2MIN-HIIT completed 3 weeks of cycling interval training, 3 days/week, consisting of either 10 × 1 min bouts at 90% PO with 1 min rests (1MIN-HIIT) or 5 × 2 min bouts with 1 min rests at undulating intensities (80%–100%) (2MIN-HIIT). Results There were no significant training effects on FM (Δ1.06 ± 1.25 kg) or %BF (Δ1.13% ± 1.88%), compared to CON. Increases in LM were not significant but increased by 1.7 kg and 2.1 kg for 1MIN and 2MIN-HIIT groups, respectively. Increases in VO2peak were also not significant for 1MIN (3.4 ml·kg−1·min−1) or 2MIN groups (2.7 ml·kg−1·min−1). IN sensitivity (HOMA-IR) improved for both training groups (Δ −2.78 ± 3.48 units; p < 0.05) compared to CON. Conclusion HIIT may be an effective short-term strategy to improve cardiorespiratory fitness and IN sensitivity in overweight males. PMID:25913937

Glucose Homeostasis and Effect of Chelation on β Cell Function in Children With β-Thalassemia Major.

PubMed

Gomber, Sunil; Dabas, Aashima; Bagmar, Shilpa; Madhu, Sri Venkata

2018-01-01

To assess the prevalence of impaired glucose tolerance in β-thalassemia major and correlate it with chelation therapy. Sixty-seven subjects with β-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.

Type 2 diabetes and hearing loss in personnel of the Self-Defense Forces.

PubMed

Sakuta, Hidenari; Suzuki, Takashi; Yasuda, Hiroko; Ito, Teizo

2007-02-01

The association of type 2 diabetes with hearing loss was evaluated in middle-aged male personnel of the Self-Defense Forces (SDFs). Hearing loss was defined as the pure-tone average (PTA) of the thresholds frequency at 0.5, 1, 2, and 4 kHz greater than 25 dB hearing levels (HL) in the worse ear. Diabetes status was determined by self-report of physician-diagnosed diabetes or by oral glucose tolerance test (OGTT). Of 699 subjects studied (age 52.9+/-1.0 years), 103 subjects were classified as having type 2 diabetes. Fasting plasma glucose of diabetic subjects was 120+/-19 mg/dl. Hearing loss levels were (worse) higher among diabetic subjects compared with subjects with normal glucose tolerance (NGT) (30.7+/-13.0 dB versus 27.4+/-12.3 dB, P=0.014). Hearing loss was more prevalent among diabetic subjects than among subjects with normal glucose tolerance (60.2% versus 45.2%, P=0.006). The odds ratio (OR) of type 2 diabetes for the presence of hearing loss was 1.87 (95% confidence interval 1.20-2.91, P=0.006) in a logistic regression analysis adjusted for age, rank, cigarette smoking and ethanol consumption. These results suggest that type 2 diabetes is associated with hearing loss independently of lifestyle factors in middle-aged men.

Comparative study of SOS2 and a novel PMP3-1 gene expression in two sunflower (Helianthus annuus L.) lines differing in salt tolerance.

PubMed

Saadia, Mubshara; Jamil, Amer; Ashraf, Muhammad; Akram, Nudrat Aisha

2013-06-01

Gene expression pattern of two important regulatory proteins, salt overly sensitive 2 (SOS2) and plasma membrane protein 3-1 (PMP3-1), involved in ion homeostasis, was analyzed in two salinity-contrasting sunflower (Helianthus annuus L.) lines, Hysun-38 (salt tolerant) and S-278 (moderately salt tolerant). The pattern was studied at selected time intervals (24 h) under 150 mM NaCl treatment. Using reverse transcription PCR, SOS2 gene fragment was obtained from young leaf and root tissues of opposing lines while that for PMP3-1 was obtained only from young root tissues. Both tolerant and moderately tolerant lines showed a gradual increase in SOS2 expression in sunflower root tissues. Leaf tissues showed the gradually increasing pattern of SOS2 expression in tolerant plants as compared to that for moderately tolerant ones that showed a relatively lower level of expression for this gene. We found the highest level of PMP 3-1 expression in the roots of tolerant sunflower line at 6 and 12 h postsalinity treatment. The moderately tolerant line showed higher expression of PMP3-1 at 12 and 24 h after salt treatment. Overall, the expression of genes for both the regulator proteins varied significantly in the two sunflower lines differing in salinity tolerance.

Tinnitus and Auditory Perception After a History of Noise Exposure: Relationship to Auditory Brainstem Response Measures.

PubMed

Bramhall, Naomi F; Konrad-Martin, Dawn; McMillan, Garnett P

2018-01-15

To determine whether auditory brainstem response (ABR) wave I amplitude is associated with measures of auditory perception in young people with normal distortion product otoacoustic emissions (DPOAEs) and varying levels of noise exposure history. Tinnitus, loudness tolerance, and speech perception ability were measured in 31 young military Veterans and 43 non-Veterans (19 to 35 years of age) with normal pure-tone thresholds and DPOAEs. Speech perception was evaluated in quiet using Northwestern University Auditory Test (NU-6) word lists and in background noise using the words in noise (WIN) test. Loudness discomfort levels were measured using 1-, 3-, 4-, and 6-kHz pulsed pure tones. DPOAEs and ABRs were collected in each participant to assess outer hair cell and auditory nerve function. The probability of reporting tinnitus in this sample increased by a factor of 2.0 per 0.1 µV decrease in ABR wave I amplitude (95% Bayesian confidence interval, 1.1 to 5.0) for males and by a factor of 2.2 (95% confidence interval, 1.0 to 6.4) for females after adjusting for sex and DPOAE levels. Similar results were obtained in an alternate model adjusted for pure-tone thresholds in addition to sex and DPOAE levels. No apparent relationship was found between wave I amplitude and either loudness tolerance or speech perception in quiet or noise. Reduced ABR wave I amplitude was associated with an increased risk of tinnitus, even after adjusting for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on tinnitus risk. This suggests that changes in peripheral input at the level of the inner hair cell or auditory nerve may lead to increases in central gain that give rise to the perception of tinnitus. Although the extent of synaptopathy in the study participants cannot be measured directly, these findings are consistent with the prediction that tinnitus may be a perceptual consequence of cochlear synaptopathy.

Performance of an open-source heart sound segmentation algorithm on eight independent databases.

PubMed

Liu, Chengyu; Springer, David; Clifford, Gari D

2017-08-01

Heart sound segmentation is a prerequisite step for the automatic analysis of heart sound signals, facilitating the subsequent identification and classification of pathological events. Recently, hidden Markov model-based algorithms have received increased interest due to their robustness in processing noisy recordings. In this study we aim to evaluate the performance of the recently published logistic regression based hidden semi-Markov model (HSMM) heart sound segmentation method, by using a wider variety of independently acquired data of varying quality. Firstly, we constructed a systematic evaluation scheme based on a new collection of heart sound databases, which we assembled for the PhysioNet/CinC Challenge 2016. This collection includes a total of more than 120 000 s of heart sounds recorded from 1297 subjects (including both healthy subjects and cardiovascular patients) and comprises eight independent heart sound databases sourced from multiple independent research groups around the world. Then, the HSMM-based segmentation method was evaluated using the assembled eight databases. The common evaluation metrics of sensitivity, specificity, accuracy, as well as the [Formula: see text] measure were used. In addition, the effect of varying the tolerance window for determining a correct segmentation was evaluated. The results confirm the high accuracy of the HSMM-based algorithm on a separate test dataset comprised of 102 306 heart sounds. An average [Formula: see text] score of 98.5% for segmenting S1 and systole intervals and 97.2% for segmenting S2 and diastole intervals were observed. The [Formula: see text] score was shown to increases with an increases in the tolerance window size, as expected. The high segmentation accuracy of the HSMM-based algorithm on a large database confirmed the algorithm's effectiveness. The described evaluation framework, combined with the largest collection of open access heart sound data, provides essential resources for evaluators who need to test their algorithms with realistic data and share reproducible results.

[PET-CT documented remission of multicentric Castleman disease after treatment with rituximab: case report and review].

PubMed

Adam, Zdeněk; Szturz, Petr; Koukalová, Renata; Řehák, Zdeněk; Pour, Luděk; Krejčí, Marta; Šmardová, Lenka; Eid, Michal; Volfová, Pavlína; Čermáková, Zdeňka; Křen, Leoš; Sokol, Filip; Hanke, Ivo; Michalková, Eva; Král, Zdeněk; Mayer, Jiří

2015-03-01

We describe a case of multicentric Castleman disease with generalized lymphadenopathy and splenomegaly, accompanied by typical B symptoms - loss of 15 kg, fever of non-infectious origin, night sweats, symptoms of anemia. Histological examination of the nodes with the highest accumulation of fluorodeoxyglucose, taken from mediastinum by thoracoscopy, revealed plasmocellular type of Castleman disease. Tests for HIV and human herpesvirus 8 (HHV-8) were negative. Three recurrences of herpes zoster indicating an alteration of immunity preceded the dia-gnosis of disease. Treatment was initiated with combination of thalidomide, dexamethasone, and cyclophosphamide. The response after 2 months therapy was not clear and patient doesn't tolerated the therapy well. Therefore, this treatment was terminated and R-CHOP (Mabthera - rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) was selected as a second-line therapy. Lymphadenopathy and splenomegaly were reduced during the 2 cycles of treatment, however, serious infectious complications accompanied the therapy. Therefore, only use of Mabthera monotherapy 375 mg /m2 was administered in 28-day intervals. This treatment has shown efficacy and tolerability. PET-CT scan has demonstrated disappearance of lymphadenopathy and splenomegaly, in addition, normalized accumulation of fluorodeoxyglucose. Monotherapy with Mabthera has proved to be effective and well tolerated drug in this case. Currently, there are more effective therapeutic alternatives in multicentric Castleman disease: treatment with monotherapy of rituximab or in combination therapy with immunomodulatory drugs (thalidomide or lenalidomide, treatment with anti-IL-6 (siltuximab) or against its receptor (tocilizumab). In the case of ineffectiveness of one treatment option must be tested other alternative. In this case the therapy based on thalidomide wasn't successful, whereas the treatment with Mabthera has achieved disappearance of disease symptoms.

Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes.

PubMed

Kim, Ye An; Ku, Eu Jeong; Khang, Ah Reum; Hong, Eun Shil; Kim, Kyoung Min; Moon, Jae Hoon; Choi, Sung Hee; Park, Kyong Soo; Jang, Hak Chul; Lim, Soo

2014-11-01

The clinical implications of prediabetes for development of type 2 diabetes may differ for Asian ethnicity. We investigated various indices derived from a 2-h oral glucose tolerance test (OGTT) in people with prediabetes to predict their future risk of diabetes. We recruited 406 consecutive subjects with prediabetes from 2005 to 2006 and followed them up every 3-6 months for up to 9 years. Prediabetes was defined as isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined glucose intolerance (CGI), or isolated elevated HbA1c (5.7-6.4%, 39-46 mmol/mol) without IFG or IGT. The rate of diabetes conversion was compared between prediabetes categories. The association of glycemic indices with development of diabetes was also investigated. Eighty-one patients were diagnosed with diabetes during the 9-year follow-up (median 46.0 months). The rate of diabetes conversion was higher in subjects with CGI (31.9%), or isolated IGT (18.5%) than in those with isolated IFG (15.2%) or isolated elevated HbA1c (10.9%). Surrogate markers reflecting β-cell dysfunction were more closely associated with diabetes conversion than insulin resistance indices. Subjects with a 30-min postload glucose ≥ 165 mg/dL and a 30-min C-peptide < 5 ng/mL had 8.83 times greater risk (95% confidence interval 2.98-26.16) of developing diabetes than other prediabetic subjects. In Asians, at least Koreans, β-cell dysfunction seems to be the major determinant for diabetes conversion. A combination of high glucose and low C-peptide levels at 30 min after OGTT may be a good predictor for diabetes conversion in this population. Copyright © 2014. Published by Elsevier Ireland Ltd.

Pregnancy Hyperglycaemia and Risk of Prenatal and Postpartum Depressive Symptoms.

PubMed

Huang, Tianyi; Rifas-Shiman, Sheryl L; Ertel, Karen A; Rich-Edwards, Janet; Kleinman, Ken; Gillman, Matthew W; Oken, Emily; James-Todd, Tamarra

2015-07-01

Glucose dysregulation in pregnancy may affect maternal depressive symptoms during the prenatal and postpartum periods via both physiologic and psychological pathways. During mid-pregnancy, a combination of 50-g 1-h non-fasting glucose challenge test (GCT) and 100-g 3-h fasting oral glucose tolerance test was used to determine pregnancy glycaemic status among women participating in Project Viva: normal glucose tolerance (NGT), isolated hyperglycaemia (IHG), impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM). Using the Edinburgh Postnatal Depression Scale (EPDS), we assessed depressive symptoms at mid-pregnancy and again at 6 months postpartum. We used logistic regression, adjusted for sociodemographic, anthropometric and lifestyle factors, to estimate the odds of elevated prenatal and postpartum depressive symptoms (EPDS ≥ 13 on 0-30 scale) in relation to GCT glucose levels and GDM status in separate models. A total of 9.6% of women showed prenatal and 8.4% postpartum depressive symptoms. Women with higher GCT glucose levels were at greater odds of elevated prenatal depressive symptoms [multivariable-adjusted odds ratio (OR) per standard deviation (SD) increase in glucose levels (27 mg/dL): 1.25; 95%: 1.07, 1.48]. Compared with NGT women, the association appeared stronger among women with IHG [OR: 1.80; 95% confidence interval (CI): 1.08, 3.00] than among those with GDM (OR: 1.45; 95% CI: 0.72, 2.91) or IGT (OR: 1.43; 95% CI: 0.59, 3.46). Neither glucose levels assessed from the GCT nor pregnancy glycaemic status were significantly associated with elevated postpartum depressive symptoms. Pregnancy hyperglycaemia was cross-sectionally associated with higher risk of prenatal depressive symptoms, but not with postpartum depressive symptoms. © 2015 John Wiley & Sons Ltd.

Butyrylcholinesterase regulates central ghrelin signaling and has an impact on food intake and glucose homeostasis.

PubMed

Chen, V P; Gao, Y; Geng, L; Brimijoin, S

2017-09-01

Ghrelin is the only orexigenic hormone known to stimulate food intake and promote obesity and insulin resistance. We recently showed that plasma ghrelin is controlled by butyrylcholinesterase (BChE), which has a strong impact on feeding and weight gain. BChE knockout (KO) mice are prone to obesity on high-fat diet, but hepatic BChE gene transfer rescues normal food intake and obesity resistance. However, these mice lack brain BChE and still develop hyperinsulinemia and insulin resistance, suggesting essential interactions between BChE and ghrelin within the brain. To test the hypothesis we used four experimental groups: (1) untreated wild-type mice, (2) BChE KO mice with LUC delivered by adeno-associated virus (AAV) in combined intravenous (i.v.) and intracerebral (i.c.) injections, (3) KO mice given AAV for mouse BChE (i.v. only) and (4) KO mice given the same vector both i.v. and i.c. All mice ate a 45% calorie high-fat diet from the age of 1 month. Body weight, body composition, daily caloric intake and serum parameters were monitored throughout, and glucose tolerance and insulin tolerance tests were performed at intervals. Circulating ghrelin levels dropped substantially in the KO mice after i.v. AAV-BChE delivery, which led to normal food intake and healthy body weight. BChE KO mice that received AAV-BChE through i.v. and i.c. combined treatments not only resisted weight gain on high-fat diet but also retained normal glucose and insulin tolerance. These data indicate a central role for BChE in regulating both insulin and glucose homeostasis. BChE gene transfer could be a useful therapy for complications linked to diet-induced obesity and insulin resistance.

Long-term tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: results from a randomised, controlled, multicentre study

PubMed Central

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-01-01

Background This study was designed to assess the long-term safety and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg, which allows management of intracyclic (breakthrough) bleeding [flexible management of intracyclic (breakthrough) bleeding (MIB)], in comparison to conventional 28-day and fixed extended regimens. Study design In this Phase III, multicentre, open-label study, women (aged 18–35 years) were randomised to EE/DRSP in the following regimens: flexibleMIB (24–120 days' active hormonal intake followed by a 4-day tablet-free interval), conventional 28-day (24 days' active hormonal intake followed by a 4-day hormone-free interval) or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval) during a 1-year comparative phase. Thereafter, women entered a 1-year safety extension phase in which the majority received the flexibleMIB regimen. Safety/tolerability outcomes were measured over 2 years. A separate analysis of certain safety parameters (endometrial, hormonal, lipid, haemostatic and metabolic variables) was conducted at two of the study centres. Results Results were analysed in 1067 and 783 women in the comparative and safety extension phases. Overall, 56.3% of women experienced ≥1 adverse event (AE) in the safety extension phase. Serious AEs occurred in 3.0%, 1.4% and 3.3% of women receiving the flexibleMIB, conventional and fixed extended regimens, respectively. No unexpected endometrial, hormonal, lipid, haemostatic or metabolic findings occurred with any of the three regimens. Conclusions EE/DRSP in a flexible extended regimen with management of intracyclic (breakthrough) bleeding is well-tolerated and, when administered for up to 2 years, has a good safety profile comparable to other estrogen/progestogen oral contraceptives. PMID:22454004

Muscle metabolic responses during high-intensity intermittent exercise measured by 31P-MRS: relationship to the critical power concept

PubMed Central

Chidnok, Weerapong; DiMenna, Fred J.; Fulford, Jonathan; Bailey, Stephen J.; Skiba, Philip F.; Vanhatalo, Anni

2013-01-01

We investigated the responses of intramuscular phosphate-linked metabolites and pH (as assessed by 31P-MRS) during intermittent high-intensity exercise protocols performed with different recovery-interval durations. Following estimation of the parameters of the power-duration relationship, i.e., the critical power (CP) and curvature constant (W′), for severe-intensity constant-power exercise, nine male subjects completed three intermittent exercise protocols to exhaustion where periods of high-intensity constant-power exercise (60 s) were separated by different durations of passive recovery (18 s, 30 s and 48 s). The tolerable duration of exercise was 304 ± 68 s, 516 ± 142 s, and 847 ± 240 s for the 18-s, 30-s, and 48-s recovery protocols, respectively (P < 0.05). The work done >CP (W>CP) was significantly greater for all intermittent protocols compared with the subjects' W′, and this difference became progressively greater as recovery-interval duration was increased. The restoration of intramuscular phosphocreatine concentration during recovery was greatest, intermediate, and least for 48 s, 30 s, and 18 s of recovery, respectively (P < 0.05). The W>CP in excess of W′ increased with greater durations of recovery, and this was correlated with the mean magnitude of muscle phosphocreatine reconstitution between work intervals (r = 0.61; P < 0.01). The results of this study show that during intermittent high-intensity exercise, recovery intervals allow intramuscular homeostasis to be restored, with the degree of restoration being related to the duration of the recovery interval. Consequently, and consistent with the intermittent CP model, the ability to perform W>CP during intermittent high-intensity exercise and, therefore, exercise tolerance, increases when recovery-interval duration is extended. PMID:24068048

Long-term use of short- and long-acting nitrates in stable angina pectoris.

PubMed

Kosmicki, Marek Antoni

2009-05-01

Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

Duration of in vivo endotoxin tolerance in horses.

PubMed

Holcombe, Susan J; Jacobs, Carrie C; Cook, Vanessa L; Gandy, Jeffery C; Hauptman, Joseph G; Sordillo, Lorraine M

2016-05-01

Endotoxemia models are used to study mechanisms and treatments of early sepsis. Repeated endotoxin exposures induce periods of endotoxin tolerance, characterized by diminished proinflammatory responses to lipopolysaccharide (LPS) and modulated production of proinflammatory cytokines. Repeated measure designs using equine endotoxemia models are rarely performed, despite the advantages associated with reduced variability, because the altered responsiveness would confound study results and because the duration of equine endotoxin tolerance is unknown. We determined the interval of endotoxin tolerance, in vivo, in horses based on physical, clinicopathologic, and proinflammatory gene expression responses to repeated endotoxin exposures. Six horses received 30 ng/kg LPS in saline infused over 30 min. Behavior pain scores, physical examination parameters, and blood for complete blood count and proinflammatory gene expression were obtained at predetermined intervals for 24h. Horses received a total of 3 endotoxin exposures. The first exposure was LPS 1, followed 7 days later by LPS 7 or 14-21 days later by LPS 14-21. Lipopolysaccharide exposures were allocated in a randomized, crossover design. Lipopolysaccharide produced clinical and clinicopathologic signs of endotoxemia and increased expression of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8, P<0.001. Horses exhibited evidence of endotoxin tolerance following LPS 7 but not following LPS 14-21. Horses had significantly lower pain scores, heart rates, respiratory rates and duration of fever, after LPS 7 compared to LPS 1 and LPS 14-21, P<0.001, and expression of TNFα was lower in the whole blood of horses after LPS 7, P=0.05. Clinical parameters and TNFα gene expression were similar or slightly increased in horses following LPS 14-21 compared to measurements made in horses following LPS 1, suggesting that endotoxin tolerance had subsided. A minimum of 3 weeks between experiments is warranted if repeated measures designs are used to assess in vivo response to endotoxin in horses. Copyright © 2016 Elsevier B.V. All rights reserved.

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males.

PubMed

de Souza, Jorge F T; Dáttilo, Murilo; de Mello, Marco T; Tufik, Sergio; Antunes, Hanna K M

2017-01-01

Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT) is emerging as a potential strategy. Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation. Method: Eleven healthy male volunteers were recruited, aged 18-35 years, who declared taking 7-8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition), 24 h of total sleep deprivation ( SD condition), HIIT training followed by regular sleep (HIIT+RS condition), and HIIT training followed by 24 h of total sleep deprivation (HIIT+ SD condition). They performed six training sessions over 2 weeks and each session consisted of 8-12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT), were performed. Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids. Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition.

The association between brain-derived neurotrophic factor and central pulse pressure after an oral glucose tolerance test.

PubMed

Lee, I-Te; Chen, Chen-Huan; Wang, Jun-Sing; Fu, Chia-Po; Lee, Wen-Jane; Liang, Kae-Woei; Lin, Shih-Yi; Sheu, Wayne Huey-Herng

2018-01-01

Arterial stiffening blunts postprandial vasodilatation. We hypothesized that brain-derived neurotrophic factor (BDNF) may modulate postprandial central pulse pressure, a surrogate marker for arterial stiffening. A total of 82 non-diabetic subjects received a 75-g oral glucose tolerance test (OGTT) after overnight fasting. Serum BDNF concentrations were determined at 0, 30, and 120min to calculate the area under the curve (AUC). Brachial and central blood pressures were measured using a noninvasive central blood pressure monitor before blood withdrawals at 0 and 120min. With the median AUC of BDNF of 45(ng/ml)∗h as the cutoff value, the central pulse pressure after glucose intake was significantly higher in the subjects with a low BDNF than in those with a high BDNF (63±16 vs. 53±11mmHg, P=0.003), while the brachial pulse pressure was not significantly different between the 2 groups (P=0.099). In a multivariate linear regression model, a lower AUC of BDNF was an independent predictor of a higher central pulse pressure after oral glucose intake (linear regression coefficient-0.202, 95% confidence interval-0.340 to -0.065, P=0.004). After oral glucose challenge, a lower serum BDNF response is significantly associated with a higher central pulse pressure. Copyright © 2017 Elsevier B.V. All rights reserved.

LEGO plot for simultaneous application of multiple quality requirements during trueness verification of quantitative laboratory tests.

PubMed

Park, Hae-il; Chae, Hyojin; Kim, Myungshin; Lee, Jehoon; Kim, Yonggoo

2014-03-01

We developed a two-dimensional plot for viewing trueness that takes into account potential shift and variable quality requirements to verify trueness using certified reference material (CRM). Glucose, total cholesterol (TC), and creatinine levels were determined by two kinds of assay in two levels of a CRM. Available quality requirements were collected, codified, and sorted in an ascending order in the plot's header row. Centering on the mean of measured values from CRM, the "mean ± US CLIA '88 allowable total error" was located in the header of the leftmost and rightmost columns. Twenty points were created in intervening columns as potential shifts. Uncertainties were calculated according to regression between certified values and uncertainties of CRM, and positioned in the corresponding columns. Cells were assigned different colors where column and row intersected based on comparison of the 95% confidence interval of the percentage bias with each quality requirement. A glucose assay failed to meet the highest quality criteria, for which shift of +0.13-0.14 mmol/l was required. A TC assay met the quality requirement and a shift of ±0.03 mmol/l was tolerable. A creatinine assay also met the quality requirement but any shift was not tolerable. The plot provides a systematic view of the trueness of quantitative laboratory tests. © 2014 Wiley Periodicals, Inc.

Genetic analysis of tolerance to the root lesion nematode Pratylenchus neglectus in the legume Medicago littoralis.

PubMed

Oldach, Klaus H; Peck, David M; Nair, Ramakrishnan M; Sokolova, Maria; Harris, John; Bogacki, Paul; Ballard, Ross

2014-04-17

The nematode Pratylenchus neglectus has a wide host range and is able to feed on the root systems of cereals, oilseeds, grain and pasture legumes. Under the Mediterranean low rainfall environments of Australia, annual Medicago pasture legumes are used in rotation with cereals to fix atmospheric nitrogen and improve soil parameters. Considerable efforts are being made in breeding programs to improve resistance and tolerance to Pratylenchus neglectus in the major crops wheat and barley, which makes it vital to develop appropriate selection tools in medics. A strong source of tolerance to root damage by the root lesion nematode (RLN) Pratylenchus neglectus had previously been identified in line RH-1 (strand medic, M. littoralis). Using RH-1, we have developed a single seed descent (SSD) population of 138 lines by crossing it to the intolerant cultivar Herald. After inoculation, RLN-associated root damage clearly segregated in the population. Genetic analysis was performed by constructing a genetic map using simple sequence repeat (SSR) and gene-based SNP markers. A highly significant quantitative trait locus (QTL), QPnTolMl.1, was identified explaining 49% of the phenotypic variation in the SSD population. All SSRs and gene-based markers in the QTL region were derived from chromosome 1 of the sequenced genome of the closely related species M. truncatula. Gene-based markers were validated in advanced breeding lines derived from the RH-1 parent and also a second RLN tolerance source, RH-2 (M. truncatula ssp. tricycla). Comparative analysis to sequenced legume genomes showed that the physical QTL interval exists as a synteny block in Lotus japonicus, common bean, soybean and chickpea. Furthermore, using the sequenced genome information of M. truncatula, the QTL interval contains 55 genes out of which five are discussed as potential candidate genes responsible for the mapped tolerance. The closely linked set of SNP-based PCR markers is directly applicable to select for two different sources of RLN tolerance in breeding programs. Moreover, genome sequence information has allowed proposing candidate genes for further functional analysis and nominates QPnTolMl.1 as a target locus for RLN tolerance in economically important grain legumes, e.g. chickpea.

Testing the air pollution tolerances of shade tree cultivars

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

Karnosky, D.J.

1978-01-01

A program in progress to test the relative air pollution tolerances of some commonly planted shade tree cultivars is described. The relative sulfur dioxide and ozone tolerances of several cultivars of acer, fagus, fraxinus, ginkgo, gleditsia, platanus, and quercus species are being determined by examination of foliar response to short-term, high-concentration fumigations. In a follow-up study, the extent of foliar injury, growth reduction, and mortality caused by air pollution will be examined for the same cultivars grown in test plantings in and around New York City. The correlation of the relative sulfur dioxide and ozone tolerances, as determined by themore » controlled-fumigation tests, with urban survival and growth will be useful in determining the adequacy of acute exposure fumigations in testing the air pollution tolerances of the tree species under study.« less

Investigation of reliability attributes and accelerated stress factors on terrestrial solar cells

NASA Technical Reports Server (NTRS)

Lathrop, J. W.; Prince, J. L.

1980-01-01

Three tasks were undertaken to investigate reliability attributes of terrestrial solar cells: (1) a study of the electrical behavior of cells in the second (reverse) quadrant; (2) the accelerated stress testing of three new state-of-the-art cells; and (3) the continued bias-temperature testing of four block 2 type silicon cells at 78 C and 135 C. Electrical characteristics measured in the second quadrant were determined to be a function of the cell's thermal behavior with breakdown depending on the initiation of localized heating. This implied that high breakdown cells may be more fault tolerant when forced to operate in the second quadrant, a result contrary to conventional thinking. The accelerated stress tests used in the first (power) quadrant were bias-temperature, bias-temperature-humidity, temperature-humidity, thermal shock, and thermal cycle. The new type cells measured included an EFG cell, a polycrystalline cell, and a Czochralski cell. Significant differences in the response to the various tests were observed between cell types. A microprocessed controlled, short interval solar cell tester was designed and construction initiated on a prototype.

Role of self-reported individual differences in preference for and tolerance of exercise intensity in fitness testing performance.

PubMed

Hall, Eric E; Petruzzello, Steven J; Ekkekakis, Panteleimon; Miller, Paul C; Bixby, Walter R

2014-09-01

Performance in fitness tests could depend on factors beyond the bioenergetic and skeletomuscular systems, such as individual differences in preference for and tolerance of different levels of exercise-induced somatosensory stimulation. Although such individual-difference variables could play a role in exercise testing and prescription, they have been understudied. The purpose of these studies was to examine the relationships of self-reported preference for and tolerance of exercise intensity with performance in fitness tests. Participants in study I were 516 men and women volunteers from a campus community, and participants in study II were 42 men recruit firefighters undergoing a 6-week training program. Both the Preference and Tolerance scores exhibited significant relationships with performance in several fitness tests and with body composition and physical activity participation. Preference and Tolerance did not change after the training program in study II, despite improvements in objective and perceived fitness, supporting their conceptualization as dispositional traits. Preference and Tolerance scores could be useful not only in ameliorating the current understanding of the determinants of physical performance, but also in personalizing exercise prescriptions and, thus, delivering exercise experiences that are more pleasant, tolerable, and sustainable.

Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949.

PubMed

Stalder, Anna K; Lott, Dominik; Strasser, Daniel S; Cruz, Hans G; Krause, Andreas; Groenen, Peter M A; Dingemanse, Jasper

2017-03-01

The main objectives of these two phase I studies were to investigate safety and tolerability as well as the pharmacokinetic/pharmacodynamic profile of the novel potent and selective formyl peptide receptor type 2 (FPR2)/Lipoxin A 4 receptor (ALX) agonist ACT-389949. A challenge model was used to assess the drug's anti-inflammatory potential, with the aim of selecting a dosing regimen for future patient studies. Two double-blind, randomized phase I studies investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of ACT-389949 at different doses and dosing regimens. Drug exposure was correlated with target engagement markers such as receptor internalization and cytokine measurements. The effect of FPR2/ALX agonism on neutrophil migration was studied in a lipopolysaccharide (LPS) inhalation model. ACT-389949 was well tolerated. Maximum concentrations were reached around 2 h after dosing, with a mean terminal half-life of 29.3 h [95% confidence interval (CI) 25.5, 33.7]. After multiple-dose administration, exposure increased by 111% (95% CI 89, 136), indicating drug accumulation. Administration of ACT-389949 resulted in a dose-dependent, long-lasting internalization of FPR2/ALX into leukocytes. Pro- and anti-inflammatory cytokines were dose-dependently but transiently upregulated only after the first dose. No pharmacological effect on neutrophil count was observed in the LPS challenge test performed at steady state. FPR2/ALX agonism with ACT-389949 was shown to be safe and well tolerated in healthy subjects. Receptor internalization and downstream mediators pointed towards a desensitization of the system, which may explain the lack of effect on neutrophil recruitment in the LPS challenge model. © 2016 The British Pharmacological Society.

Risk factors associated with abnormal glucose tolerance in the early postpartum period among Japanese women with gestational diabetes.

PubMed

Kugishima, Yukari; Yasuhi, Ichiro; Yamashita, Hiroshi; Fukuda, Masashi; Kuzume, Akiko; Sugimi, So; Umezaki, Yasushi; Suga, Sachie; Kusuda, Nobuko

2015-04-01

To identify the risk factors associated with abnormal glucose tolerance (AGT) on the first postpartum oral glucose tolerance test (OGTT) among Japanese women with gestational diabetes (GDM). In a retrospective study, data were analyzed from women with GDM who underwent their first postpartum OGTT 6-8weeks post partum at a center in Omura, Japan, between January 1, 2007, and December 31, 2011. Women with diabetes or impaired glucose tolerance were deemed to have postpartum AGT. The association between postpartum AGT and various risk factors was analyzed. Among 169 women who underwent a postpartum OGTT, 58 (34.3%) had AGT. The significant risk factors associated with postpartum AGT in univariate analysis were pre-pregnancy body mass index (P=0.096), 1-hour plasma glucose (P=0.006), hemoglobin A1c (P<0.001), insulinogenic index (P=0.05), an insulinogenic index of less than 0.4 (P=0.006), and insulin therapy during pregnancy (P<0.001). Independent risk factors identified by multivariate logistic regression models were insulinogenic index (odds ratio [OR] 0.10, 95% confidence interval [CI] 0.01-0.74; P=0.002), an insulinogenic index of less than 0.4 (OR 5.70, 95% CI 1.69-21.66; P=0.005), and insulin therapy during pregnancy (OR 3.43, 95% CI 1.03-12.55; P=0.044). Among Japanese women with GDM, a lower insulinogenic index and use of insulin therapy during pregnancy are associated with early postpartum AGT. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Evaluation of the pharmacokinetic and pharmacodynamic drug interactions between cilnidipine and valsartan, in healthy volunteers

PubMed Central

Lee, Jieon; Lee, Howard; Jang, Kyungho; Lim, Kyoung Soo; Shin, Dongseong; Yu, Kyung-Sang

2014-01-01

Purpose Although cilnidipine and valsartan are widely coadministered to patients with hypertension, their drug–drug interaction potential has not been investigated. This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and tolerability profiles of cilnidipine and valsartan, both alone and in combination, in healthy male subjects. Patients and methods Fifty-four subjects, enrolled into an open-label, single-dose, three-treatment, three-period crossover study, randomly received cilnidipine (10 mg), valsartan (160 mg), or both according to one of six sequences. Blood samples were collected at baseline and up to 24 hours after drug administration in each period. Plasma concentrations of cilnidipine and valsartan were determined by liquid chromatography with tandem mass spectrometry. Maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to the last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated by assessing adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests. Blood pressure was also measured for PD assessment. Results A total of 51 subjects completed the study. The PK profile of cilnidipine was not significantly affected by coadministered valsartan; the geometric mean ratio and 90% confidence interval (90% CI) of AUClast for cilnidipine with and without valsartan was 1.04 (0.98–1.10). Likewise, cilnidipine did not affect the PK of valsartan; the geometric mean ratio (90% CI) of AUClast for valsartan with and without cilnidipine was 0.94 (0.83–1.07). Coadministration of cilnidipine and valsartan reduced blood pressure in an additive way. No serious AEs were reported, and both cilnidipine and valsartan were well tolerated. Conclusion Coadministered cilnidipine and valsartan do not cause a significant PK or PD interaction, and they are well tolerated. PMID:25336921

Normative data for distal line bisection and baking tray task.

PubMed

Facchin, Alessio; Beschin, Nicoletta; Pisano, Alessia; Reverberi, Cristina

2016-09-01

Line bisection is one of the tests used to diagnose unilateral spatial neglect (USN). Despite its wide application, no procedure or norms were available for the distal variant when the task was performed at distance with a laser pointer. Furthermore, the baking tray task was an ecological test aimed at diagnosing USN in a more natural context. The aim of this study was to collect normative values for these two tests in an Italian population. We recruited a sample of 191 healthy subjects with ages ranging from 20 to 89 years. They performed line bisection with a laser pointer on three different line lengths (1, 1.5, and 2 m) at a distance of 3 m. After this task, the subjects performed the baking tray task and a second repetition of line bisection to test the reliability of measurement. Multiple regression analysis revealed no significant effects of demographic variables on the performance of both tests. Normative cut-off values for the two tests were developed using non-parametric tolerance intervals. The results formed the basis for clinical use of these two tools for assessing lateralized performance of patients with brain injury and for diagnosing USN.

Effect of Exercise Training and +Gz Acceleration Training on Men

NASA Technical Reports Server (NTRS)

Greenleaf, John E.; Simonson, Shawn R.; Stocks, Jodie M.; Evans, Joyce; Knapp, Charles F.; Cowell, Stephenie A.; Pemberton, Kendra N.; Wilson, Heather W.; Vener, Jamie M.; Evetts, Simon N.

2001-01-01

Countermeasures for reduction in work capacity (maximal oxygen uptake and strength) during spaceflight and enhanced orthostatic intolerance during re-entry, landing and egress from the return vehicle are continuing problems. The purpose for this study was to test the hypothesis that passive-acceleration training; supine, interval, exercise plus acceleration training and exercise combined with acceleration training would improve orthostatic tolerance in ambulatory men; and that addition of the aerobic exercise conditioning would not alter this improved tolerance from that of passive-acceleration training. Seven men (24-38 yr) underwent "Passive" training on the Ames human-powered centrifuge (HPC) for 30 min, "Exercise" training on the cycle ergometer with constant +Gz acceleration; and "Combined" exercise training at 40% to 90% of the HPC +Gz(max) exercise level. Maximal supine exercise loads increased significant (P<0.05) by 8.3% (Passive), 12.6% (Exercise), and by 15.4% (Combined) after training, but their post-training maximal oxygen uptakes and maximal heart rates were unchanged. Maximal time to fatigue (endurance) was unchanged with Passive was increased (P<0.05) with Exercise and Combined training. Thus, the exercise in the Exercise and Combined training Phases resulted in greater maximal loads and endurance without effect on maximal oxygen uptake or heart rate. There was a 4% to 6% increase (P<0.05) in all four quadriceps muscle volumes (right and left) after post-Combined training. Resting pre-tilt heart rate was elevated by 12.9% (P<0.05) only after Passive training suggesting that the exercise training attenuated the HR response. Plasma volume (% Delta) was uniformly decreased by 8% to 14% (P<0.05) at tilt-tolerance pre- vs. post-training indicating essentially no effect of training on the level of hypovolemia. Post-training tilt-tolerance time and heart rate were increased (P<0.05) only with Passive training by 37.8% and by 29.1%, respectively. Thus, addition of exercise training appeared to attenuate the increased Passive tilt-tolerance.

A comparative pharmacokinetic and tolerability analysis of the novel orotic acid salt form of tenofovir disoproxil and the fumaric acid salt form in healthy subjects

PubMed Central

Kim, Yu Kyong; Choi, Mun Ju; Oh, Tae Young; Yu, Kyung-Sang; Lee, SeungHwan

2017-01-01

A novel orotic acid salt form of tenofovir disoproxil (DA-2802) was developed and is expected to replace the fumaric acid salt form. The pharmacokinetic (PK) characteristics and tolerability profiles of DA-2802 were compared to those of tenofovir disoproxil fumarate (TDF, Viread®) in healthy subjects. A randomized, open-label, single-dose study was conducted in 36 healthy subjects using a two-treatment, two-period, and two-sequence crossover design. Subjects received a single oral dose of 319 mg DA-2802 or 300 mg TDF, during each period, with a 7-day washout. Serial blood samples were collected pre-dosing and up to 72 hours post-dosing in each period, for determination of serum tenofovir concentration, which was measured by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental method was used to obtain PK parameters of tenofovir. For comparison between the two tenofovir disoproxil salts, the 90% confidence intervals (90% CIs) of geometric mean ratios of DA-2802 to TDF for the maximum concentration (Cmax) and the area under the concentration–time curve to the last quantifiable concentration (AUC0–t) were determined. The tolerability profiles of tenofovir were assessed by evaluation of adverse events and vital signs, physical examination, ECG, and clinical laboratory tests. The serum tenofovir concentration–time profiles of DA-2802 or TDF were comparable in 32 subjects who completed the study. In both profiles, a two-compartmental elimination with first-order elimination kinetics in the terminal phase was reported in a few subjects, showing a secondary peak in the initial phase of elimination. The geometric mean ratio (90% CI) of DA-2802 to TDF was 0.898 (0.815–0.990) for Cmax and 0.904 (0.836–0.978) for AUC0–t. There were no clinically significant findings in the tolerability assessments. DA-2802 showed comparable PK characteristics and tolerability profiles to TDF. PMID:29158663

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

PubMed

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

2013-12-09

To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

PubMed Central

Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John JV; Califf, Robert M

2013-01-01

Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Setting NAVIGATOR trial. Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. Trial registration ClinicalTrials.gov NCT00097786. PMID:24322398

Tolerance of Erythrocytes in Poultry: Induction and Specificity

PubMed Central

Mitchison, N. A.

1962-01-01

Measurement of the rate of elimination of 51Cr-labelled erythrocytes provides a reliable test of immunity in fowls. Chickens can be rendered tolerant of homologous and turkey erythrocytes, as judged by this test, by receiving a series of transfusions of irradiated blood. The series were arranged so that foreign cells remained present in the circulation from the time of hatching. Tolerance induced by this treatment is generally incomplete, but can last indefinitely. In some chickens the manifestation of tolerance of turkey erythrocytes is delayed, probably because of passive transmission of antibody from the dam. Chickens old enough to react against small transfusions of homologous blood can still be rendered tolerant by massive transfusions. Tolerance of the erythrocytes from an individual donor extends only slightly to those from other donors. Tolerance acquired in this way, through transfusion of irradiated blood, stands in contrast to the more stable and complete tolerance that can be acquired through administration of viable cells. Viable cells, on the other hand, provide a less sensitive test, for birds which tolerate skin homografts often eliminate rapidly erythrocytes from the same donor. PMID:14474652

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

PubMed

London, Andrew; Jensen, Jeffrey T

2016-07-01

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency.

PubMed

di Iorgi, Natascia; Napoli, Flavia; Allegri, Anna; Secco, Andrea; Calandra, Erika; Calcagno, AnnaLisa; Frassinetti, Costanza; Ghezzi, Michele; Ambrosini, Linda; Parodi, Stefano; Gastaldi, Roberto; Loche, Sandro; Maghnie, Mohamad

2010-05-01

The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. This was a prospective study conducted in two Pediatric Endocrinology Centers. Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.

A pilot study examining the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular risk factors in cancer survivors.

PubMed

Toohey, Kellie; Pumpa, Kate L; Arnolda, Leonard; Cooke, Julie; Yip, Desmond; Craft, Paul S; Semple, Stuart

2016-01-01

The aim of this study was to evaluate the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular disease risk factors in cancer survivors. Cancer survivors within 24 months post-diagnosis were randomly assigned into the low-volume high-intensity interval training group ( n  = 8) or the continuous low to moderate intensity training group ( n  = 8) group for 36 sessions (12 weeks) of supervised exercise. The low-volume high-intensity interval training (LVHIIT) group performed 7 × 30 s intervals (≥85% maximal heart rate) and the continuous low to moderate intensity training (CLMIT) group performed continuous aerobic training for 20 min (≤55% maximal heart rate) on a stationary bike or treadmill. Significant improvements (time) were observed for 13 of the 23 dependent variables (ES 0.05-0.61, p  ≤ 0.05). An interaction effect was observed for six minute walk test (18.53% [32.43-4.63] ES 0.50, p  ≤ 0.01) with the LVHIIT group demonstrating greater improvements. These preliminary findings suggest that both interventions can induce improvements in quality of life, functional capacity and selected cardiovascular disease risk factors. The LVHIIT program was well tolerated by the participants and our results suggest that LVHIIT is the preferred modality to improve fitness (6MWT); it remains to be seen which intervention elicits the most clinically relevant outcomes for patients. A larger sample size with a control group is required to confirm the significance of these findings.

A pilot study examining the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular risk factors in cancer survivors

PubMed Central

Pumpa, Kate L.; Arnolda, Leonard; Cooke, Julie; Yip, Desmond; Craft, Paul S.; Semple, Stuart

2016-01-01

Purpose The aim of this study was to evaluate the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular disease risk factors in cancer survivors. Methods Cancer survivors within 24 months post-diagnosis were randomly assigned into the low-volume high-intensity interval training group (n = 8) or the continuous low to moderate intensity training group (n = 8) group for 36 sessions (12 weeks) of supervised exercise. The low-volume high-intensity interval training (LVHIIT) group performed 7 × 30 s intervals (≥85% maximal heart rate) and the continuous low to moderate intensity training (CLMIT) group performed continuous aerobic training for 20 min (≤55% maximal heart rate) on a stationary bike or treadmill. Results Significant improvements (time) were observed for 13 of the 23 dependent variables (ES 0.05–0.61, p ≤ 0.05). An interaction effect was observed for six minute walk test (18.53% [32.43–4.63] ES 0.50, p ≤ 0.01) with the LVHIIT group demonstrating greater improvements. Conclusion These preliminary findings suggest that both interventions can induce improvements in quality of life, functional capacity and selected cardiovascular disease risk factors. The LVHIIT program was well tolerated by the participants and our results suggest that LVHIIT is the preferred modality to improve fitness (6MWT); it remains to be seen which intervention elicits the most clinically relevant outcomes for patients. A larger sample size with a control group is required to confirm the significance of these findings. PMID:27781180

WIPCast: Probabilistic Forecasting for Aviation Decision Aid Applications

DTIC Science & Technology

2011-06-01

traders, or families planning an outing – manage weather-related risk. By quantifying risk , probabilistic forecasting enables optimization of actions via...confidence interval to the user’s risk tolerance helps drive highly effective and innovative decision support mechanisms for visually quantifying risk for

Influences on cocaine tolerance assessed under a multiple conjunctive schedule of reinforcement.

PubMed

Yoon, Jin Ho; Branch, Marc N

2009-11-01

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate-decreasing effects of cocaine that has been dependent on schedule-parameter size in the context of fixed-ratio (FR) schedules, but not under the context of fixed-interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key-pecking responses of White Carneau pigeons maintained under a three-component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose-effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response-rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule-parameter-specific tolerance. Tolerance to cocaine was generally independent of FI-parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.

Damage tolerance certification of a fighter horizontal stabilizer

NASA Astrophysics Data System (ADS)

Huang, Jia-Yen; Tsai, Ming-Yang; Chen, Jong-Sheng; Ong, Ching-Long

1995-05-01

A review of the program for the damage tolerance certification test of a composite horizontal stabilizer (HS) of a fighter is presented. The object of this program is to certify that the fatigue life and damage tolerance strength of a damaged composite horizontal stabilizer meets the design requirements. According to the specification for damage tolerance certification, a test article should be subjected to two design lifetimes of flight-by-flight load spectra simulating the in-service fatigue loading condition for the aircraft. However, considering the effect of environmental change on the composite structure, one additional lifetime test was performed. In addition, to evaluate the possibilities for extending the service life of the structure, one more lifetime test was carried out with the spectrum increased by a factor of 1.4. To assess the feasibility and reliability of repair technology on a composite structure, two damaged areas were repaired after two lifetimes of damage tolerance test. On completion of four lifetimes of the damage tolerance test, the static residual strength was measured to check whether structural strength after repair met the requirements. Stiffness and static strength of the composite HS with and without damage were evaluated and compared.

Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis

PubMed Central

Huang, Yuli; Cai, Xiaoyan; Mai, Weiyi; Li, Meijun

2016-01-01

Objectives To evaluate associations between different definitions of prediabetes and the risk of cardiovascular disease and all cause mortality. Design Meta-analysis of prospective cohort studies. Data sources Electronic databases (PubMed, Embase, and Google Scholar). Selection criteria Prospective cohort studies from general populations were included for meta-analysis if they reported adjusted relative risks with 95% confidence intervals for associations between the risk of composite cardiovascular disease, coronary heart disease, stroke, all cause mortality, and prediabetes. Review methods Two authors independently reviewed and selected eligible studies, based on predetermined selection criteria. Prediabetes was defined as impaired fasting glucose according to the criteria of the American Diabetes Association (IFG-ADA; fasting glucose 5.6-6.9 mmol/L), the WHO expert group (IFG-WHO; fasting glucose 6.1-6.9 mmol/L), impaired glucose tolerance (2 hour plasma glucose concentration 7.8-11.0 mmol/L during an oral glucose tolerance test), or raised haemoglobin A1c (HbA1c) of 39-47 mmol/mol(5.7-6.4%) according to ADA criteria or 42-47 mmol/mol (6.0-6.4%) according to the National Institute for Health and Care Excellence (NICE) guideline. The relative risks of all cause mortality and cardiovascular events were calculated and reported with 95% confidence intervals. Results 53 prospective cohort studies with 1 611 339 individuals were included for analysis. The median follow-up duration was 9.5 years. Compared with normoglycaemia, prediabetes (impaired glucose tolerance or impaired fasting glucose according to IFG-ADA or IFG-WHO criteria) was associated with an increased risk of composite cardiovascular disease (relative risk 1.13, 1.26, and 1.30 for IFG-ADA, IFG-WHO, and impaired glucose tolerance, respectively), coronary heart disease (1.10, 1.18, and 1.20, respectively), stroke (1.06, 1.17, and 1.20, respectively), and all cause mortality (1.13, 1.13 and 1.32, respectively). Increases in HBA1c to 39-47 mmol/mol or 42-47 mmol/mol were both associated with an increased risk of composite cardiovascular disease (1.21 and 1.25, respectively) and coronary heart disease (1.15 and 1.28, respectively), but not with an increased risk of stroke and all cause mortality. Conclusions Prediabetes, defined as impaired glucose tolerance, impaired fasting glucose, or raised HbA1c, was associated with an increased risk of cardiovascular disease. The health risk might be increased in people with a fasting glucose concentration as low as 5.6 mmol/L or HbA1c of 39 mmol/mol. PMID:27881363

Rapid Inpatient Titration of Intravenous Treprostinil for Pulmonary Arterial Hypertension: Safe and Tolerable.

PubMed

El-Kersh, Karim; Ruf, Kathryn M; Smith, J Shaun

There is no standard protocol for intravenous treprostinil dose escalation. In most cases, slow up-titration is performed in the outpatient setting. However, rapid up-titration in an inpatient setting is an alternative that provides opportunity for aggressive treatment of common side effects experienced during dose escalation. In this study, we describe our experience with inpatient rapid up-titration of intravenous treprostinil. This was a single-center, retrospective study in which we reviewed the data of subjects with pulmonary arterial hypertension treated at our center who underwent inpatient rapid up-titration of intravenous treprostinil. Our treprostinil dose escalation protocol included initiation at 2 ng·kg·min with subsequent up-titration by 1 ng·kg·min every 6 to 8 hours as tolerated by side effects. A total of 16 subjects were identified. Thirteen subjects were treprostinil naive (naive group), and 3 subjects were receiving subcutaneous treprostinil but were hospitalized for further intravenous up-titration of treprostinil dose (nonnaive group). In the naive group, the median maximum dose achieved was 20 ng·kg·min with an interquartile range (IQR) of 20-23 ng·kg·min. The median up-titration interval was 6 days (IQR: 4-9). In the nonnaive group, the median maximum dose achieved was 20 ng·kg·min (range: 17-30). The median up-titration interval was 8.5 days (range: 1.5-11). Overall, the median maximum dose achieved was 20 ng·kg·min (IQR: 20-23.5), and the median up-titration interval was 6 days (IQR: 4.6-9.25), with no reported significant adverse hemodynamic events. In patients with pulmonary arterial hypertension, rapid inpatient titration of intravenous treprostinil is safe and tolerable.

High-resolution genetic linkage mapping, high-temperature tolerance and growth-related quantitative trait locus (QTL) identification in Marsupenaeus japonicus.

PubMed

Lu, Xia; Luan, Sheng; Hu, Long Yang; Mao, Yong; Tao, Ye; Zhong, Sheng Ping; Kong, Jie

2016-06-01

The Kuruma prawn, Marsupenaeus japonicus, is one of the most promising marine invertebrates in the industry in Asia, Europe and Australia. However, the increasing global temperatures result in considerable economic losses in M. japonicus farming. In the present study, to select genetically improved animals for the sustainable development of the Kuruma prawn industry, a high-resolution genetic linkage map and quantitative trait locus (QTL) identification were performed using the RAD technology. The maternal map contained 5849 SNP markers and spanned 3127.23 cM, with an average marker interval of 0.535 cM. Instead, the paternal map contained 3927 SNP markers and spanned 3326.19 cM, with an average marker interval of 0.847 cM. The consensus map contained 9289 SNP markers and spanned 3610.90 cM, with an average marker interval of 0.388 cM and coverage of 99.06 % of the genome. The markers were grouped into 41 linkage groups in the maps. Significantly, negative correlation was detected between high-temperature tolerance (UTT) and body weight (BW). The QTL mapping revealed 129 significant QTL loci for UTT and four significant QTL loci for BW at the genome-wide significance threshold. Among these QTLs, 129 overlapped with linked SNPs, and the remaining four were located in regions between contiguous SNPs. They explained the total phenotypic variance ranging from 8.9 to 12.4 %. Because of a significantly negative correlation between growth and high-temperature tolerance, we demonstrate that this high-resolution linkage map and QTLs would be useful for further marker-assisted selection in the genetic improvement of M. japonicus.

Cohort Profile: Mysore Parthenon Birth Cohort

PubMed Central

Krishnaveni, Ghattu V; Veena, Sargoor R; Hill, Jacqueline C; Karat, Samuel C; Fall, Caroline HD

2015-01-01

The Mysore Parthenon Birth Cohort was established to examine the long-term effects of maternal glucose tolerance and nutritional status on cardiovascular disease risk factors in the offspring. During 1997–98, 830 of 1233 women recruited from the antenatal clinics of the Holdsworth Memorial Hospital (HMH), Mysore, India, underwent an oral glucose tolerance test. Of these, 667 women delivered live babies at HMH. Four babies with major congenital anomalies were excluded, and the remaining 663 were included for further follow-up. The babies had detailed anthropometry at birth and at 6–12-monthly intervals subsequently. Detailed cardiovascular investigations were done at ages 5, 9.5 and 13.5 years in the children, and in the parents at the 5-year and 9.5-year follow-ups. This ongoing study provides extensive data on serial anthropometry and body composition, physiological and biochemical measures, dietary intake, nutritional status, physical activity measures, stress reactivity measures and cognitive function, and socio-demographic parameters for the offspring. Data on anthropometry, cardiovascular risk factors and nutritional status are available for mothers during pregnancy. Anthropometry and risk factor measures are available for both parents at follow-up. PMID:24609067

Using string alignment in a query-by-humming system for real world applications

NASA Astrophysics Data System (ADS)

Sailer, Christian

2005-09-01

Though query by humming (i.e., retrieving music or information about music by singing a characteristic melody) has been a popular research topic during the past decade, few approaches have reached a level of usefulness beyond mere scientific interest. One of the main problems is the inherent contradiction between error tolerance and dicriminative power in conventional melody matching algorithms that rely on a melody contour approach to handle intonation or transcription errors. Adopting the string matching/alignment techniques from bioinformatics to melody sequences allows to directly assess the similarity between two melodies. This method takes an MPEG-7 compliant melody sequence (i.e., a list of note intervals and length ratios) as query and evaluates the steps necessary to transform it into the reference sequence. By introducing a musically founded cost-of-replace function and an adequate post processing, this method yields a measure for melodic similarity. Thus it is possible to construct a query by humming system that can properly discriminate between thousands of melodies and still be sufficiently error tolerant to be used by untrained singers. The robustness has been verified in extensive tests and real world applications.

Prediabetes in patients receiving tacrolimus in the first year after kidney transplantation: a prospective and multicenter study.

PubMed

Porrini, Esteban; Moreno, Jose Manuel; Osuna, Antonio; Benitez, Rocio; Lampreabe, Ildefonso; Diaz, Juan Manuel; Silva, Irene; Domínguez, Rosa; Gonzalez-Cotorruelo, Julio; Bayes, Beatriz; Lauzurica, Ricardo; Ibernon, Meritxell; Moreso, Francisco; Delgado, Patricia; Torres, Armando

2008-04-27

Tacrolimus-based immunosuppression, the most widely used regimen in kidney transplantation, increases the risk of new onset diabetes after transplantation (NODAT). However, the prevalence, evolution and risk factors of different prediabetic alterations: impaired fasting glucose, impaired glucose tolerance, and provisional diabetes, have not been established. In this multicenter and prospective study we evaluated 154 nondiabetic kidney transplant recipients receiving tacrolimus, mycophenolate mofetil and low dose steroids. An oral glucose tolerance test was performed 3 and 12 months after transplantation and prediabetes was defined by American Diabetes Association criteria. Prediabetes was highly prevalent and showed little variation between 3 and 12 months (36% and 33%, respectively). Impaired glucose tolerance was the most frequent abnormality observed (23% and 25%, respectively) observed. In addition, 20% of recipients showed NODAT by 1 year. Multivariate analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.004-1.14), pretransplant body mass index (OR: 1.3, CI: 1.09-1.6) and triglyceride/high density lipoprotein-cholesterol ratio, a marker of insulin resistance, (OR: 1.4, CI: 1.05-1.9) were independent risk factors for prediabetes. One in two recipients with tacrolimus-based immunosuppresion showed prediabetes or NODAT by 1 year posttransplantation when properly investigated. Older age and high pretransplant body mass index and triglyceride/high density lipoprotein-cholesterol ratio were risk factors for prediabetes. These findings may help applying early interventions to prevent the disorder.

Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects.

PubMed

Miller, Ann K; Harrell, Emma; Ye, Li; Baptiste-Brown, Sharon; Kleim, Jőrg-Peter; Ohrt, Colin; Duparc, Stephan; Möhrle, Jörg J; Webster, Alison; Stinnett, Sandra; Hughes, Arlene; Griffith, Sandy; Beelen, Andrew P

2013-12-01

The long-acting 8-aminoquinoline tafenoquine (TQ) coadministered with chloroquine (CQ) may radically cure Plasmodium vivax malaria. Coadministration therapy was evaluated for a pharmacokinetic interaction and for pharmacodynamic, safety and tolerability characteristics. Healthy subjects, 18-55 years old, without documented glucose-6-phosphate dehydrogenase deficiency, received CQ alone (days 1-2, 600 mg; and day 3, 300 mg), TQ alone (days 2 and 3, 450 mg) or coadministration therapy (day 1, CQ 600 mg; day 2, CQ 600 mg + TQ 450 mg; and day 3, CQ 300 mg + TQ 450 mg) in a randomized, double-blind, parallel-group study. Blood samples for pharmacokinetic and pharmacodynamic analyses and safety data, including electrocardiograms, were collected for 56 days. The coadministration of CQ + TQ had no effect on TQ AUC0-t , AUC0-∞ , Tmax or t1/2 . The 90% confidence intervals of CQ + TQ vs. TQ for AUC0-t , AUC0-∞ and t1/2 indicated no drug interaction. On day 2 of CQ + TQ coadministration, TQ Cmax and AUC0-24 increased by 38% (90% confidence interval 1.27, 1.64) and 24% (90% confidence interval 1.04, 1.46), respectively. The pharmacokinetics of CQ and its primary metabolite desethylchloroquine were not affected by TQ. Coadministration had no clinically significant effect on QT intervals and was well tolerated. No clinically significant safety or pharmacokinetic/pharmacodynamic interactions were observed with coadministered CQ and TQ in healthy subjects. © 2013 The British Pharmacological Society.

Mapping of a major QTL for salt tolerance of mature field-grown maize plants based on SNP markers.

PubMed

Luo, Meijie; Zhao, Yanxin; Zhang, Ruyang; Xing, Jinfeng; Duan, Minxiao; Li, Jingna; Wang, Naishun; Wang, Wenguang; Zhang, Shasha; Chen, Zhihui; Zhang, Huasheng; Shi, Zi; Song, Wei; Zhao, Jiuran

2017-08-15

Salt stress significantly restricts plant growth and production. Maize is an important food and economic crop but is also a salt sensitive crop. Identification of the genetic architecture controlling salt tolerance facilitates breeders to select salt tolerant lines. However, the critical quantitative trait loci (QTLs) responsible for the salt tolerance of field-grown maize plants are still unknown. To map the main genetic factors contributing to salt tolerance in mature maize, a double haploid population (240 individuals) and 1317 single nucleotide polymorphism (SNP) markers were employed to produce a genetic linkage map covering 1462.05 cM. Plant height of mature maize cultivated in the saline field (SPH) and plant height-based salt tolerance index (ratio of plant height between saline and control fields, PHI) were used to evaluate salt tolerance of mature maize plants. A major QTL for SPH was detected on Chromosome 1 with the LOD score of 22.4, which explained 31.2% of the phenotypic variation. In addition, the major QTL conditioning PHI was also mapped at the same position on Chromosome 1, and two candidate genes involving in ion homeostasis were identified within the confidence interval of this QTL. The detection of the major QTL in adult maize plant establishes the basis for the map-based cloning of genes associated with salt tolerance and provides a potential target for marker assisted selection in developing maize varieties with salt tolerance.

Circle-16QAM for a zero-guard-interval CO-OFDM system

NASA Astrophysics Data System (ADS)

Kong, Lingyu; Yang, Aiying; Guo, Peng; Lu, Yueming; Qiao, Yaojun

2018-01-01

In this paper, we introduce circle 16 quadrature amplitude modulation (C-16QAM) modulation format in a high spectral efficiency zero-guard-interval (ZGI) coherent optical (CO) orthogonal frequency-division multiplexing (OFDM) system. At transmitter, the C-16QAM has advantages over the conventional square 16QAM in terms of transmission distance and tolerance to laser linewidth and fiber nonlinearities. ZGI CO-OFDM enables to take away the cyclic prefix (CP), so it has the benefit of higher spectral efficiency compared with the conventional CO-OFDM system. At receiver, in order to compensate chromatic dispersion (CD) and phase noise in a single channel ZGI CO-OFDM system, we studied the overlapped frequency domain equalizer (OFDE) and two carrier phase recovery (CPR) algorithms. We simulate the above systems and the results demonstrate that with the C-16QAM, a 28GBaud ZGI CO-OFDM system can have the longer transmission distance, the higher tolerance to laser linewidth and fiber nonlinearities with contrast to the conventional square 16QAM.

Statistical summaries of fatigue data for design purposes

NASA Technical Reports Server (NTRS)

Wirsching, P. H.

1983-01-01

Two methods are discussed for constructing a design curve on the safe side of fatigue data. Both the tolerance interval and equivalent prediction interval (EPI) concepts provide such a curve while accounting for both the distribution of the estimators in small samples and the data scatter. The EPI is also useful as a mechanism for providing necessary statistics on S-N data for a full reliability analysis which includes uncertainty in all fatigue design factors. Examples of statistical analyses of the general strain life relationship are presented. The tolerance limit and EPI techniques for defining a design curve are demonstrated. Examples usng WASPALOY B and RQC-100 data demonstrate that a reliability model could be constructed by considering the fatigue strength and fatigue ductility coefficients as two independent random variables. A technique given for establishing the fatigue strength for high cycle lives relies on an extrapolation technique and also accounts for "runners." A reliability model or design value can be specified.

Personalized glucose-insulin model based on signal analysis.

PubMed

Goede, Simon L; de Galan, Bastiaan E; Leow, Melvin Khee Shing

2017-04-21

Glucose plasma measurements for diabetes patients are generally presented as a glucose concentration-time profile with 15-60min time scale intervals. This limited resolution obscures detailed dynamic events of glucose appearance and metabolism. Measurement intervals of 15min or more could contribute to imperfections in present diabetes treatment. High resolution data from mixed meal tolerance tests (MMTT) for 24 type 1 and type 2 diabetes patients were used in our present modeling. We introduce a model based on the physiological properties of transport, storage and utilization. This logistic approach follows the principles of electrical network analysis and signal processing theory. The method mimics the physiological equivalent of the glucose homeostasis comprising the meal ingestion, absorption via the gastrointestinal tract (GIT) to the endocrine nexus between the liver, pancreatic alpha and beta cells. This model demystifies the metabolic 'black box' by enabling in silico simulations and fitting of individual responses to clinical data. Five-minute intervals MMTT data measured from diabetic subjects result in two independent model parameters that characterize the complete glucose system response at a personalized level. From the individual data measurements, we obtain a model which can be analyzed with a standard electrical network simulator for diagnostics and treatment optimization. The insulin dosing time scale can be accurately adjusted to match the individual requirements of characterized diabetic patients without the physical burden of treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is high-intensity interval training a time-efficient exercise strategy to improve health and fitness?

PubMed

Gillen, Jenna B; Gibala, Martin J

2014-03-01

Growing research suggests that high-intensity interval training (HIIT) is a time-efficient exercise strategy to improve cardiorespiratory and metabolic health. "All out" HIIT models such as Wingate-type exercise are particularly effective, but this type of training may not be safe, tolerable or practical for many individuals. Recent studies, however, have revealed the potential for other models of HIIT, which may be more feasible but are still time-efficient, to stimulate adaptations similar to more demanding low-volume HIIT models and high-volume endurance-type training. As little as 3 HIIT sessions per week, involving ≤10 min of intense exercise within a time commitment of ≤30 min per session, including warm-up, recovery between intervals and cool down, has been shown to improve aerobic capacity, skeletal muscle oxidative capacity, exercise tolerance and markers of disease risk after only a few weeks in both healthy individuals and people with cardiometabolic disorders. Additional research is warranted, as studies conducted have been relatively short-term, with a limited number of measurements performed on small groups of subjects. However, given that "lack of time" remains one of the most commonly cited barriers to regular exercise participation, low-volume HIIT is a time-efficient exercise strategy that warrants consideration by health practitioners and fitness professionals.

Glucose ingestion causes cardiac repolarization disturbances in type 1 long QT syndrome patients and healthy subjects.

PubMed

Hyltén-Cavallius, Louise; Iepsen, Eva W; Christiansen, Michael; Graff, Claus; Linneberg, Allan; Pedersen, Oluf; Holst, Jens J; Hansen, Torben; Torekov, Signe S; Kanters, Jørgen K

2017-08-01

Both hypoglycemia and severe hyperglycemia constitute known risk factors for cardiac repolarization changes potentially leading to malignant arrhythmias. Patients with loss of function mutations in KCNQ1 are characterized by long QT syndrome (LQTS) and may be at increased risk for glucose-induced repolarization disturbances. The purpose of this study was to test the hypothesis that KCNQ1 LQTS patients are at particular risk for cardiac repolarization changes during the relative hyperglycemia that occurs after an oral glucose load. Fourteen KCNQ1 LQTS patients and 28 control participants matched for gender, body mass index, and age underwent a 3-hour oral 75-g glucose tolerance test with ECGs obtained at 7 time points. Fridericia corrected QT interval (QTcF), Bazett corrected QT interval (QTcB), and the Morphology Combination Score (MCS) were calculated. QTc and MCS increased in both groups. MCS remained elevated until 150 minutes after glucose ingestion, and the maximal change from baseline was larger among KCNQ1 LQTS patients compared with control subjects (0.28 ± 0.27 vs 0.15 ± 0.13; P <.05). Relative hyperglycemia induced by ingestion of 75-g glucose caused cardiac repolarization disturbances that were more severe in KCNQ1 LQTS patients compared with control subjects. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Protocol for diversion of confirmed positive bulk raw milk tankers to calf ranches - A review of the Pharmacokinetics of tetracyclines and sulfonamides in veal calves.

PubMed

DeDonder, K D; Gehring, R; Tell, L A; Riviere, J E

2016-12-01

The tetracyclines (TTC) and sulfonamides are among the most common residues found in bulk raw milk samples. Detection of drug residues in bulk milk (BM) tankers demonstrates that the product is not suitable for human consumption. Discarding BM with residue-contaminated milk is a waste of a valuable commodity, and a repurposing for consumption at calf ranches is a way to recapture some value. However, if calves consuming milk with drug residues are slaughtered for veal, their meat could contain drug residues. The objective of this review is to provide a residue avoidance strategy for TTC and sulfonamide residues in veal. To determine the pharmacokinetic properties of each drug a structured review of the literature was performed and the study inclusion criteria were that the publication used dairy breed calves, with body weight <330 kg or <6 months of age. The most pertinent parameters were determined to be plasma, tissue elimination half-lives, and systemic bioavailability. The results of this review were integrated with milk and tissue testing levels of quantification and tissue tolerances to formulate a recommended withdrawal interval for calves ingesting this milk. The suggested withdrawal interval of 20 days will ensure that no veal calves will test positive for residues from being fed this milk.

Lower Leg Injury Reference Values and Risk Curves from Survival Analysis for Male and Female Dummies: Meta-analysis of Postmortem Human Subject Tests.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Banerjee, Anjishnu

2015-01-01

Derive lower leg injury risk functions using survival analysis and determine injury reference values (IRV) applicable to human mid-size male and small-size female anthropometries by conducting a meta-analysis of experimental data from different studies under axial impact loading to the foot-ankle-leg complex. Specimen-specific dynamic peak force, age, total body mass, and injury data were obtained from tests conducted by applying the external load to the dorsal surface of the foot of postmortem human subject (PMHS) foot-ankle-leg preparations. Calcaneus and/or tibia injuries, alone or in combination and with/without involvement of adjacent articular complexes, were included in the injury group. Injury and noninjury tests were included. Maximum axial loads recorded by a load cell attached to the proximal end of the preparation were used. Data were analyzed by treating force as the primary variable. Age was considered as the covariate. Data were censored based on the number of tests conducted on each specimen and whether it remained intact or sustained injury; that is, right, left, and interval censoring. The best fits from different distributions were based on the Akaike information criterion; mean and plus and minus 95% confidence intervals were obtained; and normalized confidence interval sizes (quality indices) were determined at 5, 10, 25, and 50% risk levels. The normalization was based on the mean curve. Using human-equivalent age as 45 years, data were normalized and risk curves were developed for the 50th and 5th percentile human size of the dummies. Out of the available 114 tests (76 fracture and 38 no injury) from 5 groups of experiments, survival analysis was carried out using 3 groups consisting of 62 tests (35 fracture and 27 no injury). Peak forces associated with 4 specific risk levels at 25, 45, and 65 years of age are given along with probability curves (mean and plus and minus 95% confidence intervals) for PMHS and normalized data applicable to male and female dummies. Quality indices increased (less tightness-of-fit) with decreasing age and risk level for all age groups and these data are given for all chosen risk levels. These PMHS-based probability distributions at different ages using information from different groups of researchers constituting the largest body of data can be used as human tolerances to lower leg injury from axial loading. Decreasing quality indices (increasing index value) at lower probabilities suggest the need for additional tests. The anthropometry-specific mid-size male and small-size female mean human risk curves along with plus and minus 95% confidence intervals from survival analysis and associated IRV data can be used as a first step in studies aimed at advancing occupant safety in automotive and other environments.

Contraceptive efficacy and tolerability of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study.

PubMed

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-04-01

The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexible(MIB)) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18-35 years) to the following regimens: flexible(MIB) (24-120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexible(MIB) only). Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexible(MIB) vs the conventional regimen [41.0±29.1 (95% CI 38.8-43.3) vs 65.8±27.0 (95% CI 62.2-69.4) days, p<0.0001; treatment difference -24.8 (95% CI -29.2 to -20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9-67.9) days. The Pearl Index for the flexible(MIB) regimen was 0.64 (95% CI 0.28-1.26). All regimens had comparable tolerability profiles. EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexible(MIB) also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexible(MIB) regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding.

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males

PubMed Central

de Souza, Jorge F. T.; Dáttilo, Murilo; de Mello, Marco T.; Tufik, Sergio; Antunes, Hanna K. M.

2017-01-01

Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT) is emerging as a potential strategy. Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation. Method: Eleven healthy male volunteers were recruited, aged 18–35 years, who declared taking 7–8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition), 24 h of total sleep deprivation (SD condition), HIIT training followed by regular sleep (HIIT+RS condition), and HIIT training followed by 24 h of total sleep deprivation (HIIT+SD condition). They performed six training sessions over 2 weeks and each session consisted of 8–12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT), were performed. Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids. Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition. PMID:29270126

Parameter Transient Behavior Analysis on Fault Tolerant Control System

NASA Technical Reports Server (NTRS)

Belcastro, Christine (Technical Monitor); Shin, Jong-Yeob

2003-01-01

In a fault tolerant control (FTC) system, a parameter varying FTC law is reconfigured based on fault parameters estimated by fault detection and isolation (FDI) modules. FDI modules require some time to detect fault occurrences in aero-vehicle dynamics. This paper illustrates analysis of a FTC system based on estimated fault parameter transient behavior which may include false fault detections during a short time interval. Using Lyapunov function analysis, the upper bound of an induced-L2 norm of the FTC system performance is calculated as a function of a fault detection time and the exponential decay rate of the Lyapunov function.

Minimax rational approximation of the Fermi-Dirac distribution.

PubMed

Moussa, Jonathan E

2016-10-28

Accurate rational approximations of the Fermi-Dirac distribution are a useful component in many numerical algorithms for electronic structure calculations. The best known approximations use O(log(βΔ)log(ϵ -1 )) poles to achieve an error tolerance ϵ at temperature β -1 over an energy interval Δ. We apply minimax approximation to reduce the number of poles by a factor of four and replace Δ with Δ occ , the occupied energy interval. This is particularly beneficial when Δ ≫ Δ occ , such as in electronic structure calculations that use a large basis set.

Minimax rational approximation of the Fermi-Dirac distribution

NASA Astrophysics Data System (ADS)

Moussa, Jonathan E.

2016-10-01

Accurate rational approximations of the Fermi-Dirac distribution are a useful component in many numerical algorithms for electronic structure calculations. The best known approximations use O(log(βΔ)log(ɛ-1)) poles to achieve an error tolerance ɛ at temperature β-1 over an energy interval Δ. We apply minimax approximation to reduce the number of poles by a factor of four and replace Δ with Δocc, the occupied energy interval. This is particularly beneficial when Δ ≫ Δocc, such as in electronic structure calculations that use a large basis set.

Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

PubMed

Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

2008-02-01

Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, P<0.001). However, the correlation between ISF and capillary glucose levels was lower during the first hour than that in the later time period (r=0.722 vs r=0.830), and the ISF glucose levels in 69.62% of children were higher than baseline levels in the initial 1-3 hours. In 79 obese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

Single Fasting Plasma Glucose Versus 75-g Oral Glucose-Tolerance Test in Prediction of Adverse Perinatal Outcomes: A Cohort Study.

PubMed

Shen, Songying; Lu, Jinhua; Zhang, Lifang; He, Jianrong; Li, Weidong; Chen, Niannian; Wen, Xingxuan; Xiao, Wanqing; Yuan, Mingyang; Qiu, Lan; Cheng, Kar Keung; Xia, Huimin; Mol, Ben Willem J; Qiu, Xiu

2017-02-01

There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes. We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22-28weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT. 1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30-1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1h, and 2h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P=0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥5.1mmol/l), irrespective of 1h or 2h glucose levels. A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

An optimized implementation of a fault-tolerant clock synchronization circuit

NASA Technical Reports Server (NTRS)

Torres-Pomales, Wilfredo

1995-01-01

A fault-tolerant clock synchronization circuit was designed and tested. A comparison to a previous design and the procedure followed to achieve the current optimization are included. The report also includes a description of the system and the results of tests performed to study the synchronization and fault-tolerant characteristics of the implementation.

Genetic analysis of tolerance to the root lesion nematode Pratylenchus neglectus in the legume Medicago littoralis

PubMed Central

2014-01-01

Background The nematode Pratylenchus neglectus has a wide host range and is able to feed on the root systems of cereals, oilseeds, grain and pasture legumes. Under the Mediterranean low rainfall environments of Australia, annual Medicago pasture legumes are used in rotation with cereals to fix atmospheric nitrogen and improve soil parameters. Considerable efforts are being made in breeding programs to improve resistance and tolerance to Pratylenchus neglectus in the major crops wheat and barley, which makes it vital to develop appropriate selection tools in medics. Results A strong source of tolerance to root damage by the root lesion nematode (RLN) Pratylenchus neglectus had previously been identified in line RH-1 (strand medic, M. littoralis). Using RH-1, we have developed a single seed descent (SSD) population of 138 lines by crossing it to the intolerant cultivar Herald. After inoculation, RLN-associated root damage clearly segregated in the population. Genetic analysis was performed by constructing a genetic map using simple sequence repeat (SSR) and gene-based SNP markers. A highly significant quantitative trait locus (QTL), QPnTolMl.1, was identified explaining 49% of the phenotypic variation in the SSD population. All SSRs and gene-based markers in the QTL region were derived from chromosome 1 of the sequenced genome of the closely related species M. truncatula. Gene-based markers were validated in advanced breeding lines derived from the RH-1 parent and also a second RLN tolerance source, RH-2 (M. truncatula ssp. tricycla). Comparative analysis to sequenced legume genomes showed that the physical QTL interval exists as a synteny block in Lotus japonicus, common bean, soybean and chickpea. Furthermore, using the sequenced genome information of M. truncatula, the QTL interval contains 55 genes out of which five are discussed as potential candidate genes responsible for the mapped tolerance. Conclusion The closely linked set of SNP-based PCR markers is directly applicable to select for two different sources of RLN tolerance in breeding programs. Moreover, genome sequence information has allowed proposing candidate genes for further functional analysis and nominates QPnTolMl.1 as a target locus for RLN tolerance in economically important grain legumes, e.g. chickpea. PMID:24742262

Relationship between major dietary patterns and metabolic syndrome among individuals with impaired glucose tolerance.

PubMed

Amini, Massoud; Esmaillzadeh, Ahmad; Shafaeizadeh, Shila; Behrooz, Jhila; Zare, Maryam

2010-10-01

Dietary habits have been associated with the prevalence of the metabolic syndrome and limited data are available in this field for individuals with impaired glucose tolerance. This study focused on the association between major dietary patterns and prevalence of the metabolic syndrome in individuals with impaired glucose tolerance. This cross-sectional study was done in 425 subjects 35 to 55 y of age. Dietary data were collected using a food-frequency questionnaire. Blood pressure, waist circumference, glucose, triacylglycerols, and high-density lipoprotein cholesterol were measured and metabolic syndrome was defined based on Adult Treatment Panel III guidelines. Five major dietary patterns were found: a western pattern (high in sweets, butter, soda, mayonnaise, sugar, cookies, tail of a lamb, hydrogenated fat, and eggs), a prudent pattern (high in fish, peas, honey, nuts, juice, dry fruits, vegetable oil, liver and organic meat, and coconuts and low in hydrogenated fat and non-leafy vegetables), a vegetarian pattern (high in potatoes, legumes, fruits rich in vitamin C, rice, green leafy vegetables, and fruits rich in vitamin A), a high-fat dairy pattern (high in high-fat yogurt and high-fat milk and low in low-fat yogurt, peas, and bread), and a chicken and plant pattern (high in chicken, fruits rich in vitamin A, green leafy vegetables, and mayonnaise and low in beef, liver, and organic meat). After adjusting for confounding variables, the western pattern was associated with greater odds of having increased triacylglycerol (odds ratio 1.76, 95% confidence interval 1.01-3.07) and blood pressure (odds ratio 2.62, 95% confidence interval 1.32-5.23). The prudent pattern was positively associated with a prevalence of low high-density lipoprotein cholesterol levels (odds ratio 0.55, 95% confidence interval 0.31-0.96). The vegetarian dietary pattern was inversely associated with a risk of an abnormal fasting blood glucose level (odds ratio 2.26, 95% confidence interval 1.25-4.06). Major dietary patterns were significantly associated with the risk of metabolic syndrome. Copyright © 2010 Elsevier Inc. All rights reserved.

Experiments in fault tolerant software reliability

NASA Technical Reports Server (NTRS)

Mcallister, David F.; Tai, K. C.; Vouk, Mladen A.

1987-01-01

The reliability of voting was evaluated in a fault-tolerant software system for small output spaces. The effectiveness of the back-to-back testing process was investigated. Version 3.0 of the RSDIMU-ATS, a semi-automated test bed for certification testing of RSDIMU software, was prepared and distributed. Software reliability estimation methods based on non-random sampling are being studied. The investigation of existing fault-tolerance models was continued and formulation of new models was initiated.

Pilot Study: Foam Wedge Chin Support Static Tolerance Testing

DTIC Science & Technology

2017-10-24

AFRL-SA-WP-SR-2017-0026 Pilot Study : Foam Wedge Chin Support Static Tolerance Testing Austin M. Fischer, BS1; William W...COVERED (From – To) April – October 2017 4. TITLE AND SUBTITLE Pilot Study : Foam Wedge Chin Support Static Tolerance Testing 5a. CONTRACT NUMBER...prototype to mitigate the increase in helmet weight and forward center of gravity. The purpose of this pilot study was to determine the feasibility and

Understanding the new HbA1c units for the diagnosis of Type 2 diabetes.

PubMed

Braatvedt, Geoff D; Cundy, Tim; Crooke, Michael; Florkowski, Chris; Mann, Jim I; Lunt, Helen; Jackson, Rod; Orr-Walker, Brandon; Kenealy, Timothy; Drury, Paul L

2012-09-21

In New Zealand laboratories the measurement of glycated haemoglobin (HbA1c) for diagnosis of diabetes is now only reported in SI units of mmol/mol. HbA1c is now recommended as the preferred test to diagnose diabetes in most circumstances. The requirement for a second positive test in asymptomatic individuals is retained. An HbA1c greater than and equal to 50 mmol/mol (repeated on a second occasion in asymptomatic patients) is diagnostic of diabetes and a value less than and equal to 40 mmol/mol represents normal glucose tolerance. For patients with an initial HbA1c result of 41-49 mmol/mol, cardiovascular risk assessment and lifestyle interventions are recommended with repeat HbA1c screening in 6-12 months. For patients whose HbA1c is less than and equal to 40 mmol/mol, repeat screening (including for CVD risk) at intermittent intervals is recommended as per published guidelines.

Relationships of self-identified cold tolerance and cold-induced vasodilatation in the finger

NASA Astrophysics Data System (ADS)

Park, Joonhee; Lee, Joo-Young

2016-04-01

This study was conducted to investigate relationships of self-identified cold tolerance and cold-induced vasodilatation (CIVD) in the finger. Nine males and 34 females participated in the following 2 tests: a CIVD test and a self-reported survey. The CIVD test was conducted 30-min cold-water immersion (3.8 ± 0.3 °C) of the middle finger at an air temperature of 27.9 ± 0.1 °C. The self-reported questionnaire consisted of 28 questions about whole and local body cold and heat tolerances. By a cluster analysis on the survey results, the participants were divided into two groups: high self-identified cold tolerance (HSCT, n = 25) and low self-identified cold tolerance (LSCT, n = 18). LSCT had lower self-identified cold tolerance ( P < 0.001), preferred hot thermal stimulation ( P = 0.006), and wore heavier clothing during daily life ( P < 0.001) than HSCT. LSCT had significantly lower maximal finger temperatures ( T max) ( P = 0.040), smaller amplitude ( P = 0.029), and delayed onset time of CIVD ( P = 0.080) when compared to HSCT. Some questions examining the self-identified cold or heat tolerance had relationships with cold tolerance index, T max, and amplitude ( P < 0.1). These results indicate that self-identified cold tolerance classified through a standardized survey could be a good index to predict physiological cold tolerance.

Relationships of self-identified cold tolerance and cold-induced vasodilatation in the finger.

PubMed

Park, Joonhee; Lee, Joo-Young

2016-04-01

This study was conducted to investigate relationships of self-identified cold tolerance and cold-induced vasodilatation (CIVD) in the finger. Nine males and 34 females participated in the following 2 tests: a CIVD test and a self-reported survey. The CIVD test was conducted 30-min cold-water immersion (3.8 ± 0.3 °C) of the middle finger at an air temperature of 27.9 ± 0.1 °C. The self-reported questionnaire consisted of 28 questions about whole and local body cold and heat tolerances. By a cluster analysis on the survey results, the participants were divided into two groups: high self-identified cold tolerance (HSCT, n = 25) and low self-identified cold tolerance (LSCT, n = 18). LSCT had lower self-identified cold tolerance (P < 0.001), preferred hot thermal stimulation (P = 0.006), and wore heavier clothing during daily life (P < 0.001) than HSCT. LSCT had significantly lower maximal finger temperatures (T max) (P = 0.040), smaller amplitude (P = 0.029), and delayed onset time of CIVD (P = 0.080) when compared to HSCT. Some questions examining the self-identified cold or heat tolerance had relationships with cold tolerance index, T max, and amplitude (P < 0.1). These results indicate that self-identified cold tolerance classified through a standardized survey could be a good index to predict physiological cold tolerance.

Studying DDT Susceptibility at Discriminating Time Intervals Focusing on Maximum Limit of Exposure Time Survived by DDT Resistant Phlebotomus argentipes (Diptera: Psychodidae): an Investigative Report.

PubMed

Rama, Aarti; Kesari, Shreekant; Das, Pradeep; Kumar, Vijay

2017-07-24

Extensive application of routine insecticide i.e., dichlorodiphenyltrichloroethane (DDT) to control Phlebotomus argentipes (Diptera: Psychodidae), the proven vector of visceral leishmaniasis in India, had evoked the problem of resistance/tolerance against DDT, eventually nullifying the DDT dependent strategies to control this vector. Because tolerating an hour-long exposure to DDT is not challenging enough for the resistant P. argentipes, estimating susceptibility by exposing sand flies to insecticide for just an hour becomes a trivial and futile task.Therefore, this bioassay study was carried out to investigate the maximum limit of exposure time to which DDT resistant P. argentipes can endure the effect of DDT for their survival. The mortality rate of laboratory-reared DDT resistant strain P. argentipes exposed to DDT was studied at discriminating time intervals of 60 min and it was concluded that highly resistant sand flies could withstand up to 420 min of exposure to this insecticide. Additionally, the lethal time for female P. argentipes was observed to be higher than for males suggesting that they are highly resistant to DDT's toxicity. Our results support the monitoring of tolerance limit with respect to time and hence points towards an urgent need to change the World Health Organization's protocol for susceptibility identification in resistant P. argentipes.

Decrement in operant performance produced by NMDA receptor antagonists in the rat: tolerance and cross-tolerance.

PubMed

Dravolina, O A; Zvartau, E E; Bespalov, A Y

2000-04-01

Current perspectives on the clinical use of NMDA receptor antagonists infer repeated administration schedules for the management of different pathological states. The development of tolerance and cross-tolerance between different NMDA receptor antagonists may be an important factor contributing to the clinical efficacy of these drugs. The present study aimed to characterize the development of tolerance and cross-tolerance to the ability of various site-selective NMDA receptor antagonists to produce a decrement of operant responding (multiple extinction 9 s fixed-interval 1-s schedule of water reinforcement). Acute administration of D-CPPen (SDZ EAA 494; 1-5.6 mg/kg), dizocilpine (MK-801; 0.03-0.3 mg/kg), memantine (0.3-17 mg/kg), ACEA-1021 (10-56 mg/kg), and eliprodil (1-30 mg/kg) differentially affected operant responding. Both increases and decreases in response rates and accuracy of responding were observed. Repeated preexposure to D-CPPen (5.6 mg/kg, once a day for 7 days) attenuated a behavioral disruption produced by an acute challenge with D-CPPen or ACEA-1021, but potentiated the effects of dizocilpine, memantine, and eliprodil. Based on the present results, one can suggest that the repeated administration of a competitive NMDA receptor antagonist differentially affects the functional activity of various sites on NMDA receptor complex.

Patient perceptions of physical and emotional discomfort related to urodynamic testing: a questionnaire-based study in men and women with and without neurologic conditions.

PubMed

Suskind, Anne M; Clemens, J Quentin; Kaufman, Samuel R; Stoffel, John T; Oldendorf, Ann; Malaeb, Bahaa S; Jandron, Teresa; Cameron, Anne P

2015-03-01

To determine predictors of physical and emotional discomfort associated with urodynamic testing in men and women both with and without neurologic conditions. An anonymous questionnaire-based study was completed by patients immediately after undergoing fluoroscopic urodynamic testing. Participants were asked questions pertaining to their perceptions of physical and emotional discomfort related to the study, their urologic and general health history, and demographics. Logistic regression was performed to determine predictors of physical and emotional discomfort. A total of 314 patients completed the questionnaire representing a response rate of 60%. Half of the respondents (50.7%) felt that the examination was neither physically nor emotionally uncomfortable, whereas 29.0% and 12.4% of respondents felt that the physical and emotional components of the examination were most uncomfortable, respectively. Placement of the urethral catheter was the most commonly reported component of physical discomfort (42.9%), whereas anxiety (27.7%) was the most commonly reported component of emotional discomfort. Presence of a neurologic problem (odds ratio, 0.273; 95% confidence interval, 0.121-0.617) and older age (odds ratio, 0.585; 95% confidence interval, 0.405-0.847) were factors associated with less physical discomfort. There were no significant predictors of emotional discomfort based on our model. Urodynamic studies were well tolerated regardless of gender. Presence of a neurologic condition and older age were predictors of less physical discomfort. These findings are useful in counseling patients regarding what to expect when having urodynamic procedures. Copyright © 2015 Elsevier Inc. All rights reserved.

40 CFR 1065.672 - Drift correction.

Code of Federal Regulations, 2013 CFR

2013-07-01

... interval gas analyzer response to the span gas concentration. x postspan = post-test interval gas analyzer... = post-test interval gas analyzer response to the zero gas concentration. Example: x refzero = 0 µmol/mol... occurred before one or more previous test intervals. (4) For any post-test interval concentrations, use...

40 CFR 1065.672 - Drift correction.

Code of Federal Regulations, 2010 CFR

2010-07-01

... interval gas analyzer response to the span gas concentration. x postspan = post-test interval gas analyzer... = post-test interval gas analyzer response to the zero gas concentration. Example: x refzero = 0 µmol/mol... occurred before one or more previous test intervals. (4) For any post-test interval concentrations, use...

40 CFR 1065.672 - Drift correction.

Code of Federal Regulations, 2014 CFR

2014-07-01

... interval gas analyzer response to the span gas concentration. x postspan = post-test interval gas analyzer... = post-test interval gas analyzer response to the zero gas concentration. Example: x refzero = 0 µmol/mol... occurred before one or more previous test intervals. (4) For any post-test interval concentrations, use...

40 CFR 1065.672 - Drift correction.

Code of Federal Regulations, 2012 CFR

2012-07-01

... interval gas analyzer response to the span gas concentration. x postspan = post-test interval gas analyzer... = post-test interval gas analyzer response to the zero gas concentration. Example: x refzero = 0 µmol/mol... occurred before one or more previous test intervals. (4) For any post-test interval concentrations, use...

40 CFR 1065.672 - Drift correction.

Code of Federal Regulations, 2011 CFR

2011-07-01

... interval gas analyzer response to the span gas concentration. x postspan = post-test interval gas analyzer... = post-test interval gas analyzer response to the zero gas concentration. Example: x refzero = 0 µmol/mol... occurred before one or more previous test intervals. (4) For any post-test interval concentrations, use...

Immunologic changes in children with egg allergy ingesting extensively heated egg.

PubMed

Lemon-Mulé, Heather; Sampson, Hugh A; Sicherer, Scott H; Shreffler, Wayne G; Noone, Sally; Nowak-Wegrzyn, Anna

2008-11-01

Prior studies have suggested that heated egg might be tolerated by some children with egg allergy. We sought to confirm tolerance of heated egg in a subset of children with egg allergy, to evaluate clinical and immunologic predictors of heated egg tolerance, to characterize immunologic changes associated with continued ingestion of heated egg, and to determine whether a diet incorporating heated egg is well tolerated. Subjects with documented IgE-mediated egg allergy underwent physician-supervised oral food challenges to extensively heated egg (in the form of a muffin and a waffle), with tolerant subjects also undergoing regular egg challenges (in a form of scrambled egg or French toast). Heated egg-tolerant subjects incorporated heated egg into their diets. Skin prick test wheal diameters and egg white, ovalbumin, and ovomucoid IgE levels, as well as ovalbumin and ovomucoid IgG4 levels, were measured at baseline for all subjects and at 3, 6, and 12 months for those tolerant of heated egg. Sixty-four of 117 subjects tolerated heated egg, 23 tolerated regular egg, and 27 reacted to heated egg. Heated egg-reactive subjects had larger skin test wheals and greater egg white-specific, ovalbumin-specific, and ovomucoid-specific IgE levels compared with heated egg- and egg-tolerant subjects. Continued ingestion of heated egg was associated with decreased skin test wheal diameters and ovalbumin-specific IgE levels and increased ovalbumin-specific and ovomucoid-specific IgG4 levels. The majority of subjects with egg allergy were tolerant of heated egg. Continued ingestion of heated egg was well tolerated and associated with immunologic changes that paralleled the changes observed with the development of clinical tolerance to regular egg.

A theory of drug tolerance and dependence I: a conceptual analysis.

PubMed

Peper, Abraham

2004-08-21

A mathematical model of drug tolerance and its underlying theory is presented. The model extends a first approach, published previously. The model is essentially more complex than the generally used model of homeostasis, which is demonstrated to fail in describing tolerance development to repeated drug administrations. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary only in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behavior to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes. In addition, it establishes a relation between the drug dose at any moment, and the resulting drug effect and relates the magnitude of the reactions following withdrawal to the rate of tolerance and other parameters involved in the tolerance process. The present paper analyses the concept behind the model. The next paper discusses the mathematical model.

SUGAR: spotting undiagnosed glucose abnormal results--a new protocol to increase postpartum testing among women with gestational diabetes mellitus.

PubMed

Carson, Michael P; Morgan, Benjamin; Gussman, Debra; Brown, Monica; Rothenberg, Karen; Wisner, Theresa A

2015-02-01

Over 70% of women with gestational diabetes mellitus (GDM) will develop diabetes mellitus (DM), but only 30% follow through with the recommended postpartum oral glucose tolerance testing (OGTT). HbA1c is approved to diagnose DM, and combined with a fasting plasma glucose it can identify 93% of patients with dysglycemia. We tested the hypothesis that a single blood draw to assess for dysglycemia at the postpartum visit could improve testing rates compared with those required to obtain an OGTT at an outside laboratory. Prospective cohort study of all women with GDM who delivered between July 2010 and December 2011. When insurance status required testing at an outside laboratory an OGTT was ordered, when insurance allowed testing at our center a random sugar and HbA1c were drawn at the postpartum visit (SUGAR Protocol). Of the 40 women, 36 attended a postpartum visit. In the SUGAR arm, 19 of 19 (100%) were tested versus 9 of 17 (53%) in the OGTT arm; relative risk of testing was 1.9 (95% confidence interval, 1.2-3.0). 36% were glucose intolerant. This pilot study found that an in-office testing model doubled the rate of postpartum testing in this clinic population, and was reasonably sensitive at detecting dysglycemia. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pharmacokinetic interactions and safety evaluations of coadministered tafenoquine and chloroquine in healthy subjects

PubMed Central

Miller, Ann K; Harrell, Emma; Ye, Li; Baptiste-Brown, Sharon; Kleim, Jőrg-Peter; Ohrt, Colin; Duparc, Stephan; Möhrle, Jörg J; Webster, Alison; Stinnett, Sandra; Hughes, Arlene; Griffith, Sandy; Beelen, Andrew P

2013-01-01

Aims The long-acting 8-aminoquinoline tafenoquine (TQ) coadministered with chloroquine (CQ) may radically cure Plasmodium vivax malaria. Coadministration therapy was evaluated for a pharmacokinetic interaction and for pharmacodynamic, safety and tolerability characteristics. Methods Healthy subjects, 18–55 years old, without documented glucose-6-phosphate dehydrogenase deficiency, received CQ alone (days 1–2, 600 mg; and day 3, 300 mg), TQ alone (days 2 and 3, 450 mg) or coadministration therapy (day 1, CQ 600 mg; day 2, CQ 600 mg + TQ 450 mg; and day 3, CQ 300 mg + TQ 450 mg) in a randomized, double-blind, parallel-group study. Blood samples for pharmacokinetic and pharmacodynamic analyses and safety data, including electrocardiograms, were collected for 56 days. Results The coadministration of CQ + TQ had no effect on TQ AUC0–t, AUC0–∞, Tmax or t1/2. The 90% confidence intervals of CQ + TQ vs. TQ for AUC0–t, AUC0–∞ and t1/2 indicated no drug interaction. On day 2 of CQ + TQ coadministration, TQ Cmax and AUC0–24 increased by 38% (90% confidence interval 1.27, 1.64) and 24% (90% confidence interval 1.04, 1.46), respectively. The pharmacokinetics of CQ and its primary metabolite desethylchloroquine were not affected by TQ. Coadministration had no clinically significant effect on QT intervals and was well tolerated. Conclusions No clinically significant safety or pharmacokinetic/pharmacodynamic interactions were observed with coadministered CQ and TQ in healthy subjects. PMID:23701202

Ultrasound-guided shoulder MR arthrography: comparison of rotator interval and posterior approach.

PubMed

Ogul, Hayri; Bayraktutan, Ummugulsum; Ozgokce, Mesut; Tuncer, Kutsi; Yuce, Ihsan; Yalcin, Ahmet; Pirimoglu, Berhan; Sagsoz, Erdem; Kantarci, Mecit

2014-01-01

The purpose of this study was to prospectively evaluate the two different ultrasound-guided injection techniques for magnetic resonance (MR) arthrography of the shoulder. This study included 100 patients [50 rotator interval group (n=50) vs. 50 posterior approach group (n=50)]. All procedures were performed by the same radiologist. The two injection techniques were compared. The discomfort during and after arthrography was evaluated. Extraarticular contrast media extravasation was graded according to the MRI findings. The number of injection attempts, effect of contrast media extravasation rate on diagnostic quality and procedure times were recorded. There were no significant difference between the posterior and rotator interval puncture groups with regard to pain (P=.915), procedure times (P=.401) or attempt scores (P=.182). There were significantly more contrast media extravasations with rotator interval approach than posterior approach (P<.05). Both techniques were successful and well tolerated by patients. Posterior injection technique provided a more effective route with decreased extravasation rate and easier approach compared to the rotator interval approach. © 2014.

Short-term therapy with combination dipeptidyl peptidase-4 inhibitor saxagliptin/metformin extended release (XR) is superior to saxagliptin or metformin XR monotherapy in prediabetic women with polycystic ovary syndrome: a single-blind, randomized, pilot study.

PubMed

Elkind-Hirsch, Karen E; Paterson, Martha S; Seidemann, Ericka L; Gutowski, Hanh C

2017-01-01

To evaluate efficacy with the dipeptidyl peptidase-4 inhibitor saxagliptin (SAXA), metformin extended release (MET), and combination (SAXA-MET) in patients with polycystic ovary syndrome (PCOS) and impaired glucose regulation. Prospective, randomized, single-blind drug study. Outpatient clinic. Patients (n = 38) with PCOS (aged 18-42 years) and prediabetic hyperglycemia determined by a 75-gram oral glucose tolerance test. Patients were randomized to SAXA-MET (5 mg/2,000 mg), SAXA (5 mg), or MET (2,000 mg) for 16 weeks. Fasting and mean blood glucose, insulin sensitivity, insulin secretion, and insulin secretion-sensitivity index (IS-SI) by oral glucose tolerance tests. Free androgen index and lipid levels, average menstrual interval, and anthropometric measurements (body mass index, waist circumference, and waist/height ratio). The study was completed by 34 patients. Nineteen patients had normal glucose tolerance: 3 of 12 (25%) on MET; 6 of 11 (55%) on SAXA; and 10 of 11 (91%) on SAXA-MET (SAXA-MET statistically superior to MET) at study completion. Body mass index, waist circumference, waist/height ratio, free androgen index, insulin sensitivity, IS-SI, and menses improved in all groups; however, IS-SI and menstrual regularity were significantly better with SAXA-MET vs. MET treatment. Triglyceride, triglyceride/high-density lipoprotein cholesterol ratio and mean blood glucose significantly declined in the SAXA-MET and SAXA groups only. This pilot work provides the first evidence regarding the effects of a dipeptidyl peptidase-4 inhibitor alone and in combination with MET in this patient population. Treatment with SAXA-MET was superior to either drug alone in terms of clinical and metabolic benefits in prediabetic patients with PCOS. NCT02022007. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Associations of circulating calcium and 25-hydroxyvitamin D with glucose metabolism in pregnancy: a cross-sectional study in European and South Asian women.

PubMed

Whitelaw, Donald C; Scally, Andrew J; Tuffnell, Derek J; Davies, T Jeffrey; Fraser, William D; Bhopal, Raj S; Wright, John; Lawlor, Debbie A

2014-03-01

Vitamin D deficiency is thought to impair insulin action and glucose metabolism; however, previous studies have not examined ethnic differences or the influence of calcium and parathyroid hormone. We investigated this in a cohort of predominantly white European and south Asian women during pregnancy. In this cross-sectional study from an urban population in northern England (53.8°N), 1467 women were recruited when undergoing glucose tolerance testing (75 g oral glucose tolerance test) at 26 weeks' gestation. Gestational diabetes mellitus (GDM) was diagnosed in 137 women (9.3%). Median 25-hydroxyvitamin D concentration for the study population was 9.3 ng/mL (interquartile range 5.2, 16.9) and was higher in European [15.2 ng/mL (10.7, 23.5)] than in south Asian women [5.9 ng/mL (3.9, 9.4), P < .001]. After appropriate adjustment for confounders, 25-hydroxyvitamin D showed a weak inverse association with fasting plasma glucose (FPG; mean difference 1.0% per 1 SD; the ratio of geometric means (RGM) 0.99, 95% confidence interval (CI) 0.98, 1.00), and PTH was weakly associated with FPG (RGM 1.01, 95% CI 1.00, 1.02), but neither was associated with fasting insulin, postchallenge glucose, or GDM. Serum calcium (albumin adjusted) was strongly associated with fasting insulin (RGM 1.06; 95% CI 1.03, 1.08), postchallenge glucose (RGM 1.03, 95% CI 1.01, 1.04), and GDM (odds ratio 1.33, 95% CI 1.06, 1.66) but not with FPG. Associations were similar in European and south Asian women. These findings do not indicate any important association between vitamin D status and glucose tolerance in pregnancy. Relationships between circulating calcium and glucose metabolism warrant further investigation.

Risk assessment and decontamination of Quinalphos under different culinary processes in/on cabbage.

PubMed

Aktar, Md Wasim; Sengupta, Dwaipayan; Purkait, Swarnali; Chowdhury, Ashim

2010-04-01

Quinalphos 20 AF was applied at the rate of 500 and 1,000 g a.i. ha(-1) in cabbage for two consecutive seasons and the samples harvested at intervals of 0 (3 h after application), 2, 4, 6, 8, and 10 days interval after application. The calculated half-life values were 1.27-1.38 days and 1.12-1.24 days for cabbage heads and cropped soil, respectively. The calculated safe waiting period based on field dissipation study was 5.28-6.7 days, which indicated its persistence nature. Thus, to reduce the safe waiting period, efforts were made to decontaminate the Quinalphos residue from cabbage head by various household preparations (viz. washing, cooking, washing plus cooking, salt water dipping, dipping in boiled salt water, dipping in detergent solution, and dipping in boiled detergent solution). Statistical analysis of the data using Duncan's multiple range test revealed that various household processing substantially reduced the residue of Quinalphos in cabbage heads in the range of 27.72-75.01% irrespective of any dose and seasons, but none were able to satisfactorily bring down the residue below the tolerance level of 0.05 mg kg(-1).

A feasible repetitive transcranial magnetic stimulation clinical protocol in migraine prevention.

PubMed

Zardouz, Shawn; Shi, Lei; Leung, Albert

2016-01-01

This case series was conducted to determine the clinical feasibility of a repetitive transcranial magnetic stimulation protocol for the prevention of migraine (with and without aura). Five patients with migraines underwent five repetitive transcranial magnetic stimulation sessions separated in 1- to 2-week intervals for a period of 2 months at a single tertiary medical center. Repetitive transcranial magnetic stimulation was applied to the left motor cortex with 2000 pulses (20 trains with 1s inter-train interval) delivered per session, at a frequency of 10 Hz and 80% resting motor threshold. Pre- and post-treatment numerical rating pain scales were collected, and percent reductions in intensity, frequency, and duration were generated. An average decrease in 37.8%, 32.1%, and 31.2% were noted in the intensity, frequency, and duration of migraines post-repetitive transcranial magnetic stimulation, respectively. A mean decrease in 1.9±1.0 (numerical rating pain scale ± standard deviation; range: 0.4-2.8) in headache intensity scores was noted after the repetitive transcranial magnetic stimulation sessions. The tested repetitive transcranial magnetic stimulation protocol is a well-tolerated, safe, and effective method for migraine prevention.

Development anmd testing of electrophoresis solutions. Task I.1: Development of optimal buffer system

NASA Technical Reports Server (NTRS)

1985-01-01

Two buffers were explored for testing: low ionic strength electrophoresis buffer with and without density gradient material. It was found that the electrophoresis routine was better tolerated when Ficoll was present. The results of a viability study of primary human fetal kidney (HFK-1) cells at the first passage are shown. Cell strain HFK-1 was used in several experiments at the first and second passage. The HFK consisted mainly of fibroblasts, and HFK-1 has a high epithelioid cell content. The chromosomes of HFK were examined and found to be euploid. The stock medium for cell electrophoresis is described. In this solution density gradient solutes such as sucrose and Ficoll are dissolved to bring the osmolarity to 0.30. Its ionic strength is less than 0.01M, and its conductivity is usually 0.0011 mho/cm. Methods for viability determination included direct microscopic counting of the percent cells attached and spread within 24 hr of plating test cultures or electrophoretically separated fractions. The Cytograf viability assay concept was tested, and shown that blue stained cells scatter less light into the 0.8 to 3.3 deg angular interval than do unstained cells.

The effects of repeated administration of camphor-crataegus berry extract combination on blood pressure and on attentional performance - a randomized, placebo-controlled, double-blind study.

PubMed

Erfurt, L; Schandry, R; Rubenbauer, S; Braun, U

2014-09-25

The present study investigated the effects of repeated administration of Korodin(®), a combination of camphor and crataegus berry extract, on blood pressure and attentional functioning. This study was conducted based on a randomized, placebo-controlled, double-blind design. 54 persons participated (33 female, 21 male) with a mean age of 24.3 years. Blood pressure and body mass index were in the normal range. Participants received 20 drops of either Korodin(®) or a placebo for four times with interjacent time intervals of about 10 min. Blood pressure was measured sphygmomanometrically before and after each administration. Attentional performance was quantified by using two paper-and-pencil tests, the d2 Test of Attention and Digit Symbol Test. Greater increases in blood pressure occurred after the four Korodin(®) administrations in comparison to the four placebo administrations. The performance in two parameters of d2 Test of Attention was consistently superior after the intake of Korodin(®). The excellent tolerability and safety of Korodin(®), even after a total consumption of 80 drops, was confirmed. Copyright © 2014 Elsevier GmbH. All rights reserved.

Self testing for diabetes mellitus.

PubMed Central

Davies, M; Alban-Davies, H; Cook, C; Day, J

1991-01-01

OBJECTIVE--To develop a simple, economically viable, and effective means of population screening for diabetes mellitus. DESIGN--A postal request system for self testing for glycosuria with foil wrapped dipsticks. Preprandial and postprandial tests were compared with a single postprandial test. The subjects were instructed how to test, and a result card was supplied on which to record and return the result. All those recording a positive test result and 50 people recording a negative result were invited for an oral glucose tolerance test. SETTING--General practice in east Suffolk, list size 11534. PATIENTS--All subjects aged 45-70 years registered with the practice were identified by Suffolk Family Health Services Authority (n = 3057). The 73 subjects known to have diabetes from the practice's register were excluded, leaving 2984 subjects, 2363 (79.2%) of whom responded. 1167 subjects completed the single test and 1196 the two tests. MAIN OUTCOME MEASURES--Response rate and number of patients with glycosuria. Sensitivity, specificity, and positive predictive value of a single postprandial test and preprandial and postprandial tests. Number of new cases of diabetes identified and cost of screening. RESULTS--Of the patients completing the single postprandial test, 29 had a positive result, an oral glucose tolerance test showed that eight (28%) had diabetes, six (21%) impaired glucose tolerance, and 14 (48%) normal glucose tolerance. 44 of the group who tested before and after eating had a positive result; nine (20%) had diabetes, five (11%) impaired tolerance, and 26 (11%) normal tolerance. Screening cost 59p per subject and 81 pounds per case detected. Of the 17 people with previously undiagnosed diabetes, eight were asymptomatic and 11 had not visited their general practitioner in the past three months. CONCLUSIONS--A postal request system for self testing for postprandial glycosuria in people aged 45-70 is a simple and effective method of population screening for diabetes mellitus. PMID:1912918

[Resistivity and hemodynamic reactions of essentially healthy pilots to the passive orthostatic test].

PubMed

Bondareva, S V; Vartbaronov, R A; Ponomarenko, K V; Bagaudinov, K G; Khomenko, M N

2009-01-01

The paper analyzes the data of expert tilt testing (-80 degrees, 20 min.) of 66 essentially healthy pilots. Hemodynamic reactions were characterized based on the standard concept of functional classes (FC). Good test tolerance was recorded in 86.4% of cases among which 36.4% were referred to FC-I and 50%--to FC-II. Adequate test tolerance (FC-II) was recorded in 10.6%; reduced and poor test tolerance (FC-IV and FC-V)--in 3%. According to ECG and computerized tachooscillography, the adaptive hemodynamic reactions were optimum in pilots of group FC-I as compared with group FC-II and all the more so when compared with FC-III. The last two groups showed some objective symptoms that had not been looked for in the past (a distinct lability of blood pressure, and incomplete hypertensive and hypotensive reactions) that differentiated these groups from FC-I. Results of the analysis made it possible to put forward additional clinical functional criteria to assess tilt tolerance of pilots with different levels of functional tolerance.

Visual working memory is more tolerant than visual long-term memory.

PubMed

Schurgin, Mark W; Flombaum, Jonathan I

2018-05-07

Human visual memory is tolerant, meaning that it supports object recognition despite variability across encounters at the image level. Tolerant object recognition remains one capacity in which artificial intelligence trails humans. Typically, tolerance is described as a property of human visual long-term memory (VLTM). In contrast, visual working memory (VWM) is not usually ascribed a role in tolerant recognition, with tests of that system usually demanding discriminatory power-identifying changes, not sameness. There are good reasons to expect that VLTM is more tolerant; functionally, recognition over the long-term must accommodate the fact that objects will not be viewed under identical conditions; and practically, the passive and massive nature of VLTM may impose relatively permissive criteria for thinking that two inputs are the same. But empirically, tolerance has never been compared across working and long-term visual memory. We therefore developed a novel paradigm for equating encoding and test across different memory types. In each experiment trial, participants saw two objects, memory for one tested immediately (VWM) and later for the other (VLTM). VWM performance was better than VLTM and remained robust despite the introduction of image and object variability. In contrast, VLTM performance suffered linearly as more variability was introduced into test stimuli. Additional experiments excluded interference effects as causes for the observed differences. These results suggest the possibility of a previously unidentified role for VWM in the acquisition of tolerant representations for object recognition. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study

PubMed Central

Douillard, J-Y; Ostoros, G; Cobo, M; Ciuleanu, T; McCormack, R; Webster, A; Milenkova, T

2014-01-01

Background: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Methods: Treatment: gefitinib 250 mg day−1 until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. Results: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8% adenocarcinoma 97.2% never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5–77.7), DCR 90.6% (95% CI 83.5–94.8), median PFS 9.7 months (95% CI 8.5–11.0), median OS 19.2 months (95% CI 17.0–NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15% SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8–74.7). Conclusion: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable. PMID:24263064

Tolerance to Non-Opioid Analgesics is Opioid Sensitive in the Nucleus Raphe Magnus.

PubMed

Tsagareli, Merab G; Nozadze, Ivliane; Tsiklauri, Nana; Gurtskaia, Gulnaz

2011-01-01

Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of tolerance. Our recent study has revealed that microinjection of three drugs analgin, ketorolac, and xefocam into the central nucleus of amygdala produce tolerance to them and cross-tolerance to morphine. Here we report that repeated administrations of these NSAIDs into the nucleus raphe magnus (NRM) in the following 4 days result in progressively less antinociception compare to the saline control, i.e., tolerance develops to these drugs in male rats. Special control experiments showed that post-treatment with the μ-opioid antagonist naloxone into the NRM significantly decreased antinociceptive effects of NSAIDs on the first day of testing in the tail-flick (TF) reflex and hot plate (HP) latency tests. On the second day, naloxone generally had trend effects in both TF and HP tests and impeded the development of tolerance to the antinociceptive effect of non-opioid analgesics. These findings strongly support the suggestion of endogenous opioid involvement in NSAIDs antinociception and tolerance in the descending pain-control system. Moreover, repeated injections of NSAIDs progressively lead to tolerance to them, cross-tolerance to morphine, and the risk of a withdrawal syndrome. Therefore, these results are important for human medicine too.

Testing For EM Upsets In Aircraft Control Computers

NASA Technical Reports Server (NTRS)

Belcastro, Celeste M.

1994-01-01

Effects of transient electrical signals evaluated in laboratory tests. Method of evaluating nominally fault-tolerant, aircraft-type digital-computer-based control system devised. Provides for evaluation of susceptibility of system to upset and evaluation of integrity of control when system subjected to transient electrical signals like those induced by electromagnetic (EM) source, in this case lightning. Beyond aerospace applications, fault-tolerant control systems becoming more wide-spread in industry; such as in automobiles. Method supports practical, systematic tests for evaluation of designs of fault-tolerant control systems.

Test and analysis results for composite transport fuselage and wing structures

NASA Technical Reports Server (NTRS)

Deaton, Jerry W.; Kullerd, Susan M.; Madan, Ram C.; Chen, Victor L.

1992-01-01

Automated tow placement (ATP) and stitching of dry textile composite preforms followed by resin transfer molding (RTM) are being studied as cost effective manufacturing processes for obtaining damage tolerant fuselage and wing structures for transport aircraft. Data are presented to assess the damage tolerance of ATP and RTM fuselage elements with stitched-on stiffeners from compression tests of impacted three J-stiffened panels and from stiffener pull-off tests. Data are also presented to assess the damage tolerance of RTM wing elements which had stitched skin and stiffeners from impacted single stiffener and three blade stiffened compression tests and stiffener pull-off tests.

Winnowing sequences from a database search.

PubMed

Berman, P; Zhang, Z; Wolf, Y I; Koonin, E V; Miller, W

2000-01-01

In database searches for sequence similarity, matches to a distinct sequence region (e.g., protein domain) are frequently obscured by numerous matches to another region of the same sequence. In order to cope with this problem, algorithms are developed to discard redundant matches. One model for this problem begins with a list of intervals, each with an associated score; each interval gives the range of positions in the query sequence that align to a database sequence, and the score is that of the alignment. If interval I is contained in interval J, and I's score is less than J's, then I is said to be dominated by J. The problem is then to identify each interval that is dominated by at least K other intervals, where K is a given level of "tolerable redundancy." An algorithm is developed to solve the problem in O(N log N) time and O(N*) space, where N is the number of intervals and N* is a precisely defined value that never exceeds N and is frequently much smaller. This criterion for discarding database hits has been implemented in the Blast program, as illustrated herein with examples. Several variations and extensions of this approach are also described.

Aniracetam and DNQX affect the acquisition of rapid tolerance to ethanol in mice.

PubMed

Rial, Daniel; Takahashi, Reinaldo Naoto; Morato, Gina Struffaldi

2009-03-01

Several studies have emphasized the role of learning in the development of rapid tolerance and have shown that glutamate-mediated neurotransmission plays an important role in this phenomenon. Since the AMPA/kainate receptor system is directly involved in plasticity mechanisms, the influence of this receptor system on rapid tolerance induced by ethanol was studied using the rotarod. In the first experiment, mice were pretreated with aniracetam, an agonist of AMPA/kainate receptors, 30 min before ethanol (2.75 g/kg; IP) treatment, and tested on the rotarod. After 24 h, the groups were tested on the rotarod under ethanol treatment. Aniracetam facilitated the acquisition of rapid tolerance to ethanol. In the second experiment, mice received DNQX, a competitive antagonist of the AMPA receptor, 30 min before ethanol treatment (3 g/kg) and submitted to the rotarod. This dose of ethanol produced tolerance per se. Groups were tested under ethanol treatment (1.75 g/kg) after 24 h. DNQX blocked rapid tolerance to ethanol. Using a similar protocol, the third experiment showed that DNQX blocked the aniracetam-induced facilitation of rapid tolerance to ethanol. Our results show that aniracetam facilitates whereas DNQX blocks ethanol tolerance, suggesting that the non-NMDA receptors are involved in this phenomenon.

Habituation of enterotoxigenic Staphylococcus aureus to Origanum vulgare L. essential oil does not induce direct-tolerance and cross-tolerance to salts and organic acids

PubMed Central

Tavares, Adassa Gama; do Monte, Daniel Farias Marinho; Albuquerque, Allan dos Reis; Sampaio, Fábio Correia; Magnani, Marciane; de Siqueira, José Pinto; de Souza, Evandro Leite

2015-01-01

Enterotoxigenic Staphylococcus aureus strains that were isolated from foods were investigated for their ability to develop direct-tolerance and cross-tolerance to sodium chloride (NaCl), potassium chloride (KCl), lactic acid (LA) and acetic acid (AA) after habituation in sublethal amounts (1/2 of the minimum inhibitory concentration - 1/2 MIC and 1/4 of the minimum inhibitory concentration - 1/4 MIC) of Origanum vulgare L. essential oil (OVEO). The habituation of S. aureus to 1/2 MIC and 1/4 MIC of OVEO did not induce direct-tolerance or cross-tolerance in the tested strains, as assessed by modulation of MIC values. Otherwise, exposing the strains to OVEO at sublethal concentrations maintained or increased the sensitivity of the cells to the tested stressing agents because the MIC values of OVEO, NaCl, KCl, LA and AA against the cells that were previously habituated to OVEO remained the same or decreased when compared with non-habituated cells. These data indicate that OVEO does not have an inductive effect on the acquisition of direct-tolerance or cross-tolerance in the tested enterotoxigenic strains of S. aureus to antimicrobial agents that are typically used in food preservation. PMID:26413067

Evaluation of Drought Tolerance of the Vietnamese Soybean Cultivars Provides Potential Resources for Soybean Production and Genetic Engineering

PubMed Central

Nguyen, Quang Thien; Hoang, Xuan Lan Thi; Thao, Nguyen Phuong; Tran, Lam-Son Phan

2014-01-01

Drought is one of the greatest constraints to soybean production in many countries, including Vietnam. Although a wide variety of the newly produced cultivars have been produced recently in Vietnam through classical breeding to cope with water shortage, little knowledge of their molecular and physiological responses to drought has been discovered. This study was conducted to quickly evaluate drought tolerance of thirteen local soybean cultivars for selection of the best drought-tolerant cultivars for further field test. Differences in drought tolerance of cultivars were assessed by root and shoot lengths, relative water content, and drought-tolerant index under both normal and drought conditions. Our data demonstrated that DT51 is the strongest drought-tolerant genotype among all the tested cultivars, while the highest drought-sensitive phenotype was observed with MTD720. Thus, DT51 could be subjected to further yield tests in the field prior to suggesting it for use in production. Due to their contrasting drought-tolerant phenotypes, DT51 and MTD720 provide excellent genetic resources for further studies underlying mechanisms regulating drought responses and gene discovery. Our results provide vital information to support the effort of molecular breeding and genetic engineering to improve drought tolerance of soybean. PMID:24804248

A phase 1, multicentre, open-label study to evaluate ovarian follicular activity and hormone levels with an extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

PubMed

Kroll, Robin; Seidman, Larry; Ricciotti, Nancy; Howard, Brandon; Weiss, Herman

2015-01-01

To evaluate the effect on ovarian follicular activity of the 91-day extended-regimen combined oral contraceptive (COC), consisting of 84 days of levonorgestrel (LNG)/ethinylestradiol (EE) 150 μg/30 μg tablets plus seven days of EE 10 μg tablets in place of placebo. This was a phase 1, open-label study. Ovarian follicular activity was classified via the Hoogland and Skouby method. Safety and tolerability as well as return to ovulation were assessed. Of the 35 subjects included in the efficacy analysis, luteinized, unruptured follicles, or ovulation were detected in 0 of 35 cycles during the first 28-day interval; 1 of 35 cycles (2.9%) in the second 28-day interval; and 2 of 35 cycles (5.7%) in the final 35-day interval. The ovarian activity rate over the entire 91-day treatment period was 2.9%. There was a low incidence of treatment-emergent adverse events. Ovulation returned in most subjects (77.1%, 27/35) within 32 days following the last dose of COC. The 91-day extended-regimen COC with low-dose EE supplementation was found to be effective in suppressing ovarian activity and inhibiting ovulation and was well tolerated. Return to ovulation was rapid, occurring within approximately one month after discontinuation of COC.

IVF cycle cost estimation using Activity Based Costing and Monte Carlo simulation.

PubMed

Cassettari, Lucia; Mosca, Marco; Mosca, Roberto; Rolando, Fabio; Costa, Mauro; Pisaturo, Valerio

2016-03-01

The Authors present a new methodological approach in stochastic regime to determine the actual costs of an healthcare process. The paper specifically shows the application of the methodology for the determination of the cost of an Assisted reproductive technology (ART) treatment in Italy. The reason of this research comes from the fact that deterministic regime is inadequate to implement an accurate estimate of the cost of this particular treatment. In fact the durations of the different activities involved are unfixed and described by means of frequency distributions. Hence the need to determine in addition to the mean value of the cost, the interval within which it is intended to vary with a known confidence level. Consequently the cost obtained for each type of cycle investigated (in vitro fertilization and embryo transfer with or without intracytoplasmic sperm injection), shows tolerance intervals around the mean value sufficiently restricted as to make the data obtained statistically robust and therefore usable also as reference for any benchmark with other Countries. It should be noted that under a methodological point of view the approach was rigorous. In fact it was used both the technique of Activity Based Costing for determining the cost of individual activities of the process both the Monte Carlo simulation, with control of experimental error, for the construction of the tolerance intervals on the final result.

Minimax rational approximation of the Fermi-Dirac distribution

DOE PAGES

Moussa, Jonathan E.

2016-10-27

Accurate rational approximations of the Fermi-Dirac distribution are a useful component in many numerical algorithms for electronic structure calculations. The best known approximations use O(log(βΔ)log(ϵ –1)) poles to achieve an error tolerance ϵ at temperature β –1 over an energy interval Δ. We apply minimax approximation to reduce the number of poles by a factor of four and replace Δ with Δ occ, the occupied energy interval. Furthermore, this is particularly beneficial when Δ >> Δ occ, such as in electronic structure calculations that use a large basis set.

Phytoremediation of Petroleum Hydrocarbon (PHC) Contaminated Soil by Using Mimosa pudica L. .

PubMed

Budhadev, Basumatary; Rubul, Saikia; Sabitry, Bordoloi; Hari Prasad, Sarma

2014-07-01

The aim of this study was to evaluate the efficiency of Mimosa pudica L. that could be effective in phytoremediation of PHC-contaminated soil. Experiments were conducted in net house to determine the tolerance of this species to a heavy crude oil contaminated soil under the application of two fertilizer levels and reduction of PHC was monitored for 180 days. Assessment of plant growth, biomass and Total Oil and Grease (TOG) degradation were carried out at an interval of 60 days. In the presence of contaminants, biomass and plant height were reduced up to 27% and 10.4% respectively. Experiments with different percentages of crude oil showed that M. pudica could tolerate crude-oil contamination up to 6.2% (w/w). The estimation of TOG in soil of the tested plants revealed that M. pudica could decrease 31.7% of crude oil contaminants in low fertilizer level (200N, 100P, 100K) and 24.7% in high fertilizer level (240N, 120P, 120K). In case of unplanted pots, the reduction of TOG was 13.7% in low fertilizer level and 11.2% in high fertilizer level. This experiment has identified the suitability of a native candidate plant species for further investigation of their phytoremediation potential.

Initiating/maintaining long-acting injectable antipsychotics in schizophrenia/schizoaffective or bipolar disorder - expert consensus survey part 2.

PubMed

Sajatovic, Martha; Ross, Ruth; Legacy, Susan N; Byerly, Matthew; Kane, John M; DiBiasi, Faith; Fitzgerald, Heather; Correll, Christoph U

2018-01-01

The aim of this study was to provide recommendations on initiating and maintaining long-acting injectable antipsychotics (LAIs) in individuals with schizophrenia/schizoaffective or bipolar disorder. A 50-question survey comprising 916 response options was completed by 34 expert researchers and high prescribers with extensive LAI experience, rating relative appropriateness/importance on a 9-point scale. Consensus was determined using chi-square test of score distributions. Results of 21 questions comprising 339 response options regarding LAI initiation, maintenance treatment, adequate trial definition, identifying treatment nonresponse, and switching are reported. Experts agreed that the most important LAI selection factor was patient response/tolerability to previous antipsychotics. An adequate therapeutic LAI trial was defined as the time to steady state ± 1-2 injection cycles. Experts suggested that oral efficacy and tolerability should be established before switching to an LAI, without consensus on the required time, and that the time for oral supplementation and next injection interval should be determined by the time to attainment of therapeutic LAI levels. Most experts agreed that ≥1 adequate LAI trial is needed to identify the lack of efficacy. There was little agreement about strategies for switching between LAIs. Expert guidance may aid clinicians in their decisions regarding initiating/maintaining LAIs in individuals with schizophrenia/schizoaffective or bipolar disorder.

Abnormal glucose tolerance post-gestational diabetes mellitus as defined by the International Association of Diabetes and Pregnancy Study Groups criteria.

PubMed

Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Saunders, Jean A; Kirwan, Breda; O'Dea, Angela; Gillespie, Paddy; Glynn, Liam G; McGuire, Brian E; O'Neill, Ciarán; O'Shea, P M; Dunne, F P

2016-10-01

An increase in gestational diabetes mellitus (GDM) prevalence has been demonstrated across many countries with adoption of the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. Here, we determine the cumulative incidence of abnormal glucose tolerance among women with previous GDM, and identify clinical risk factors predicting this. Two hundred and seventy women with previous IADPSG-defined GDM were prospectively followed up for 5years (mean 2.6) post-index pregnancy, and compared with 388 women with normal glucose tolerance (NGT) in pregnancy. Cumulative incidence of abnormal glucose tolerance (using American Diabetes Association criteria for impaired fasting glucose, impaired glucose tolerance and diabetes) was determined using the Kaplan-Meier method of survival analysis. Cox regression models were constructed to test for factors predicting abnormal glucose tolerance. Twenty-six percent of women with previous GDM had abnormal glucose tolerance vs 4% with NGT, with the log-rank test demonstrating significantly different survival curves (P<0.001). Women meeting IADPSG, but not the World Health Organization (WHO) 1999 criteria, had a lower cumulative incidence than women meeting both sets of criteria, both in the early post-partum period (4.2% vs 21.7%, P<0.001) and at longer-term follow-up (13.7% vs 32.6%, P<0.001). Predictive factors were glucose levels on the pregnancy oral glucose tolerance test, family history of diabetes, gestational week at testing, and BMI at follow-up. The proportion of women developing abnormal glucose tolerance remains high among those with IADPSG-defined GDM. This demonstrates the need for continued close follow-up, although the optimal frequency and method needs further study. © 2016 European Society of Endocrinology.

Injury tolerance of tibia for the car-pedestrian impact.

PubMed

Mo, Fuhao; Arnoux, Pierre Jean; Jure, Jean Jaques; Masson, Catherine

2012-05-01

Lower limbs are normally the first contacted body region during car-pedestrian accidents, and easily suffer serious injuries. The previous tibia bending tolerances for pedestrian safety were mainly developed from three-point bending tests on tibia mid-shaft. The tibia tolerances of other locations are still not investigated enough. In addition, tibia loading condition under the car-pedestrian impact should be explored to compare with the three-point bending. This work aims to investigate the injury tolerance of tibia fracture with combined experimental data and numerical simulation. Eleven new reported quasi-static bending tests of tibia mid-shaft, and additional eleven dynamic mid-shaft bending test results in the previous literature were used to define injury risk functions. Furthermore, to investigate the influence of tibia locations on bending tolerance, finite element simulations with lower limb model were implemented according to three-point bending and pedestrian impact conditions. The regressive curve of tibia bending tolerance was obtained from the simulations on the different impact locations, and indicated that tibia fracture tolerance could vary largely due to the impact locations for the car-pedestrian crash. Copyright © 2011 Elsevier Ltd. All rights reserved.

Challenges with nitrate therapy and nitrate tolerance: prevalence, prevention, and clinical relevance.

PubMed

Thadani, Udho

2014-08-01

Nitrate therapy has been an effective treatment for ischemic heart disease for over 100 years. The anti-ischemic and exercise-promoting benefits of sublingually administered nitrates are well established. Nitroglycerin is indicated for the relief of an established attack of angina and for prophylactic use, but its effects are short lived. In an effort to increase the duration of beneficial effects, long-acting orally administered and topical applications of nitrates have been developed; however, following their continued or frequent daily use, patients soon develop tolerance to these long-acting nitrate preparations. Once tolerance develops, patients begin losing the protective effects of the long-acting nitrate therapy. By providing a nitrate-free interval, or declining nitrate levels at night, one can overcome or reduce the development of tolerance, but cannot provide 24-h anti-anginal and anti-ischemic protection. In addition, patients may be vulnerable to occurrence of rebound angina and myocardial ischemia during periods of absent nitrate levels at night and early hours of the morning, and worsening of exercise capacity prior to the morning dose of the medication. This has been a concern with nitroglycerin patches but not with oral formulations of isosorbide-5 mononitrates, and has not been adequately studied with isosorbide dinitrate. This paper describes problems associated with nitrate tolerance, reviews mechanisms by which nitrate tolerance and loss of efficacy develop, and presents strategies to avoid nitrate tolerance and maintain efficacy when using long-acting nitrate formulations.

A theory of drug tolerance and dependence II: the mathematical model.

PubMed

Peper, Abraham

2004-08-21

The preceding paper presented a model of drug tolerance and dependence. The model assumes the development of tolerance to a repeatedly administered drug to be the result of a regulated adaptive process. The oral detection and analysis of exogenous substances is proposed to be the primary stimulus for the mechanism of drug tolerance. Anticipation and environmental cues are in the model considered secondary stimuli, becoming primary in dependence and addiction or when the drug administration bypasses the natural-oral-route, as is the case when drugs are administered intravenously. The model considers adaptation to the effect of a drug and adaptation to the interval between drug taking autonomous tolerance processes. Simulations with the mathematical model demonstrate the model's behaviour to be consistent with important characteristics of the development of tolerance to repeatedly administered drugs: the gradual decrease in drug effect when tolerance develops, the high sensitivity to small changes in drug dose, the rebound phenomenon and the large reactions following withdrawal in dependence. The present paper discusses the mathematical model in terms of its design. The model is a nonlinear, learning feedback system, fully satisfying control theoretical principles. It accepts any form of the stimulus-the drug intake-and describes how the physiological processes involved affect the distribution of the drug through the body and the stability of the regulation loop. The mathematical model verifies the proposed theory and provides a basis for the implementation of mathematical models of specific physiological processes.

Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

PubMed

Strassman, R J; Qualls, C R; Berg, L M

1996-05-01

Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

Calculation of Glucose Dose for Intraperitoneal Glucose Tolerance Tests in Lean and Obese Mice.

PubMed

Jørgensen, Mikkel S; Tornqvist, Kristina S; Hvid, Henning

2017-01-01

Glucose tolerance tests are used frequently in nonclinical research with laboratory animals, for example during characterization of obese phenotypes. Despite published standard operating procedures for glucose tolerance tests in rodents, how glucose doses should be calculated when obese and lean animals are compared is not well documented. Typically the glucose dose is calculated as 2 g/kg body weight, regardless of body composition. With this approach, obese mice receive larger glucose doses than do lean animals, potentially leading to overestimation of glucose intolerance in obese animals. In this study, we performed intraperitoneal glucose tolerance tests in mice with diet-induced obesity and their lean controls, with glucose doses based on either the total body weight or the lean body mass of the animals. To determine glucose tolerance, we determined the blood glucose AUC during the glucose tolerance test. We found that the blood glucose AUC was increased significantly in obese mice compared with lean mice by 75% on average when glucose was dosed according to the lean body mass and by 87% when the glucose dose was calculated according to total body weight. Therefore, mice with diet-induced obesity were approximately equally glucose intolerant between the 2 dose-calculation protocols. However, we recommend calculating the glucose dose according to the lean body mass of the mice, because doing so eliminates the concern regarding overdosing of obese animals.

Dynamic modelling and estimation of the error due to asynchronism in a redundant asynchronous multiprocessor system

NASA Technical Reports Server (NTRS)

Huynh, Loc C.; Duval, R. W.

1986-01-01

The use of Redundant Asynchronous Multiprocessor System to achieve ultrareliable Fault Tolerant Control Systems shows great promise. The development has been hampered by the inability to determine whether differences in the outputs of redundant CPU's are due to failures or to accrued error built up by slight differences in CPU clock intervals. This study derives an analytical dynamic model of the difference between redundant CPU's due to differences in their clock intervals and uses this model with on-line parameter identification to idenitify the differences in the clock intervals. The ability of this methodology to accurately track errors due to asynchronisity generate an error signal with the effect of asynchronisity removed and this signal may be used to detect and isolate actual system failures.

Pharmacokinetic and tolerability of i.m. disodium clodronate 200 mg/lidocaine 1%, given twice monthly, in comparison with i.m. disodium clodronate 100 mg/lidocaine 1%, given weekly, in healthy postmenopausal female patients.

PubMed

Radicioni, Milko; Cremonesi, Giovanni; Baraldi, Enrica; Leuratti, Chiara; Mariotti, Fabrizia

2013-04-01

Clodronate is a bisphosphonate effective in the prevention and treatment of osteoporosis in postmenopausal women. Non-adherence to bisphosphonates, however, is a major issue in clinical practice. Simplifying dose regimens may increase compliance. To assess bioequivalence between an intramuscular (i.m.) clodronate 200 mg/lidocaine 1% twice-a-month formulation and a clodronate 100 mg/lidocaine 1% weekly formulation in 32 postmenopausal women. In this double-blind, randomized, two-way crossover study, test and reference formulations were administered in single dose, with a 2-week wash-out between administrations. The primary endpoint was clodronic acid cumulative excretion in the first 24 hours after injection (Xu0-24h). Cumulative excretion in the 72 hours post-dose (Xu0-72h) and maximum excretion rate (Ratemax) were also evaluated. Bioequivalence was assumed if the 90% confidence intervals (CIs) of the geometric means ratios of the dose-normalized parameters were within the 80.00 - 125.00% range. Local tolerability was evaluated. Mean Xu0-24h values were 114.03 ±23.13 mg and 55.22 ±9.73 mg for clodronate 200 mg and 100 mg. The 90% CIs for dose-normalized Xu0-24h, Xu0-72h and Ratemax ere 95 -110%, 94 -107% and 95 - 113%. Local tolerability of both treatments was good. The differences in pain intensity between formulations were not sigificantly different at most assessment times. Headache was the only treatment-related adverse event. Bioequivalence of the two formulations was confirmed in terms of dose-normalized rate and amount of clodronic acid excretion. This result, together with the favorable tolerability of the novel 200 mg formulation, suggests the possibility of reducing the number of i.m. administrations from once-a-week to twice-a-month.

Associations of green tea and rock tea consumption with risk of impaired fasting glucose and impaired glucose tolerance in Chinese men and women.

PubMed

Huang, Huibin; Guo, Qiuxuan; Qiu, Changsheng; Huang, Baoying; Fu, Xianguo; Yao, Jin; Liang, Jixing; Li, Liantao; Chen, Ling; Tang, Kaka; Lin, Lixiang; Lu, Jieli; Bi, Yufang; Ning, Guang; Wen, Junping; Lin, Caijing; Chen, Gang

2013-01-01

To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association. Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1-15, 16-30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27-0.65), 0.23 (95% CI, 0.12-0.46), and 0.41 (95% CI, 0.17-0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1-15, 16-30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48-0.98), 0.59 (95% CI, 0.39-0.90), and 0.64 (95% CI, 0.43-0.97), respectively. A U-shaped association was observed, subjects who consumed 16-30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT. Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16-30 cups per week.

Associations of Green Tea and Rock Tea Consumption with Risk of Impaired Fasting Glucose and Impaired Glucose Tolerance in Chinese Men and Women

PubMed Central

Huang, Huibin; Guo, Qiuxuan; Qiu, Changsheng; Huang, Baoying; Fu, Xianguo; Yao, Jin; Liang, Jixing; Li, Liantao; Chen, Ling; Tang, Kaka; Lin, Lixiang; Lu, Jieli; Bi, Yufang; Ning, Guang; Wen, Junping; Lin, Caijing; Chen, Gang

2013-01-01

Objective To explore the associations of green tea and rock tea consumption with risk of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Methods A multistage, stratified, cluster, random-sampling method was used to select a representative sample from Fujian Province in China. In total, 4808 subjects without cardiovascular disease, hypertension, cancer, or pancreatic, liver, kidney, or gastrointestinal diseases were enrolled in the study. A standard questionnaire was used to gather data on tea (green, rock, and black) consumption and other relevant factors. The assessment of impaired glucose regulation (IGR) was using 75-g oral glucose tolerance test (OGTT), the diagnostic criteria of normal glucose tolerance was according to American Diabetes Association. Results Green tea consumption was associated with a lower risk of IFG, while rock tea consumption was associated with a lower risk of IGT. The adjusted odds ratios for IFG for green tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.42 (95% confidence intervals (CI) 0.27–0.65), 0.23 (95% CI, 0.12–0.46), and 0.41 (95% CI, 0.17–0.93), respectively. The adjusted odds ratios for IGT for rock tea consumption of <1, 1–15, 16–30, and >30 cups per week were 1.0 (reference), 0.69 (95% CI, 0.48–0.98), 0.59 (95% CI, 0.39–0.90), and 0.64 (95% CI, 0.43–0.97), respectively. A U-shaped association was observed, subjects who consumed 16–30 cups of green or rock tea per week having the lowest odds ratios for IFG or IGT. Conclusions Consumption of green or rock tea may protect against the development of type 2 diabetes mellitus in Chinese men and women, particularly in those who drink 16–30 cups per week. PMID:24260170

Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

PubMed Central

Keller, David M.; Low, David A.; Davis, Scott L.; Hastings, Jeff

2011-01-01

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ∼34°C and skin surface cooling ∼12–15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ∼30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals. PMID:21454746

Fault-tolerant onboard digital information switching and routing for communications satellites

NASA Technical Reports Server (NTRS)

Shalkhauser, Mary JO; Quintana, Jorge A.; Soni, Nitin J.; Kim, Heechul

1993-01-01

The NASA Lewis Research Center is developing an information-switching processor for future meshed very-small-aperture terminal (VSAT) communications satellites. The information-switching processor will switch and route baseband user data onboard the VSAT satellite to connect thousands of Earth terminals. Fault tolerance is a critical issue in developing information-switching processor circuitry that will provide and maintain reliable communications services. In parallel with the conceptual development of the meshed VSAT satellite network architecture, NASA designed and built a simple test bed for developing and demonstrating baseband switch architectures and fault-tolerance techniques. The meshed VSAT architecture and the switching demonstration test bed are described, and the initial switching architecture and the fault-tolerance techniques that were developed and tested are discussed.

Associations between women's perceptions of domestic violence and contraceptive use in seven countries in West and Central Africa.

PubMed

Olorunsaiye, Comfort Z; Brunner Huber, Larissa; Laditka, Sarah B; Kulkarni, Shanti; Boyd, A Suzanne

2017-10-01

This study examined associations of women's attitudes toward domestic violence (DV) and contraceptive use in West and Central Africa. We used data from the Multiple Indicator Cluster Surveys for women in seven countries in West and Central Africa (2009-2011, n=80,055). We measured contraceptive use as none, traditional, or modern contraceptives. DV approval was measured as no, low, or high tolerance of wife beating. Multinomial logistic regression estimated odds of using traditional or modern methods versus none, adjusting for age, education, wealth, residence, parity, marital structure, spousal age-difference, and religion. Many women had no or low DV tolerance (41%, 44%, respectively); most used no contraception (81%). In adjusted results, women with low DV tolerance had lower odds of using traditional contraceptive methods (odds ratio, OR=0.87; 95% confidence interval, CI: 0.78-0.98) or modern methods (OR=0.86; 95% CI: 0.78-0.95) compared to women with no tolerance. Women with high DV tolerance had 28% lower odds of traditional contraceptive use (95% CI: 0.60-0.90), and 38% lower odds of modern contraceptive use (95% CI: 0.59-0.88) compared to women with no tolerance. The high prevalence of DV approval may threaten the success of programs aimed at improving women's reproductive health, including contraceptive use. Copyright © 2017 Elsevier B.V. All rights reserved.

Yeasts associated with an abandoned mining area in Pernek and their tolerance to different chemical elements.

PubMed

Vadkertiová, Renáta; Molnárová, Jana; Lux, Alexander; Vaculík, Marek; Lišková, Desana

2016-05-01

Four plants, Cirsium arvense (creeping thistle), Equisetum arvense (field horsetail), Oxalis acetosella (wood sorrel) and Phragmites australis (common reed), which grew in an abandoned Sb-mining area in Pernek (Malé Karpaty Mts., Slovakia), were investigated for the yeast species. Yeasts were isolated from both the leaves of the plants and the soil adjacent to the plants. In total, 65 yeast cultures, belonging to 11 ascomycetous and 5 basidiomycetous yeast species, were isolated. The species most frequently isolated from both the soil and leaf samples were Trichosporon porosum, Galactomyces candidus and Candida solani, whereas Aureobasidium pullulans, Candida tsuchiyae and Sporidiobolus metaroseus were isolated exclusively from the plant leaves. All the yeast species isolated were tested for their tolerance to two heavy metals (Cd, Zn) and three metalloids (As, Sb and Si). The yeasts isolated from both the leaves and soils exhibited a high tolerance level to both As and Sb, present in elevated concentrations at the locality. Among the yeast species tested, Cryptococcus musci, a close relative to Cryptococcus humicola, was the species most tolerant to all the chemical elements tested, with the exception of Si. It grew in the presence of 200 mmol/L Zn, 200 mmol/L Cd, 60 mmol/L As and 50 mmol/L Sb, and therefore, it can be considered as a multi-tolerant species. Some of the yeast species were tolerant to the individual chemical elements. The yeast-like species Trichosporon laibachii exhibited the highest tolerance to Si of all yeasts tested, and Cryptococcus flavescens and Lindnera saturnus showed the same tolerance as Cryptococcus musci to Zn and As, respectively. The majority of the yeasts showed a notably low tolerance to Cd (not exceeded 0.5 mmol/L), which was present in small amounts in the soil. However, Candida solani, isolated from the soil, exhibited a higher tolerance to Cd (20 mmol/L) than to As (2 mmol/L).

Contraceptive efficacy and tolerability of ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen: an open-label, multicentre, randomised, controlled study

PubMed Central

Klipping, Christine; Duijkers, Ingrid; Fortier, Michel P; Marr, Joachim; Trummer, Dietmar; Elliesen, Jörg

2012-01-01

Background The contraceptive efficacy and tolerability of a new flexible extended regimen of ethinylestradiol (EE) 20 μg/drospirenone (DRSP) 3 mg to extend the menstrual cycle and enable management of intracyclic (breakthrough) bleeding (flexibleMIB) was investigated and the bleeding pattern compared with a conventional 28-day regimen and a fixed extended 124-day regimen. Study design This Phase III, 2-year, multicentre, open-label study randomly (4:1:1) allocated women (aged 18–35 years) to the following regimens: flexibleMIB (24–120 days' active hormonal intake with 4-day tablet-free intervals); conventional (24 days' active hormonal intake followed by a 4-day hormone-free interval); or fixed extended (120 days' uninterrupted active hormonal intake followed by a 4-day tablet-free interval). Primary outcomes included the number of bleeding/spotting days during Year 1 (all regimens) and the number of observed unintended pregnancies over 2 years (flexibleMIB only). Results Results were analysed in 1067 women (full analysis set). The mean number of bleeding/spotting days was lower with the flexibleMIB vs the conventional regimen [41.0±29.1 (95% CI 38.8–43.3) vs 65.8±27.0 (95% CI 62.2–69.4) days, p<0.0001; treatment difference −24.8 (95% CI −29.2 to −20.3) days]. The corresponding value for the fixed extended regimen was 60.9±51.1 (95% CI 53.9–67.9) days. The Pearl Index for the flexibleMIB regimen was 0.64 (95% CI 0.28–1.26). All regimens had comparable tolerability profiles. Conclusions EE 20 μg/DRSP 3 mg administered as a flexible extended regimen with MIB is effective, well tolerated and is associated with statistically significantly fewer bleeding/spotting days and fewer withdrawal bleeding episodes vs EE/DRSP in a conventional 28-day regimen. The flexibleMIB also provided statistically significantly fewer spotting days vs EE/DRSP in a fixed extended 124-day regimen (post hoc evaluation). The flexibleMIB regimen allows women to extend their menstrual cycle and manage their intracyclic (breakthrough) bleeding. PMID:22454003

Murine Lupus Susceptibility Locus Sle2 Activates DNA-Reactive B Cells through Two Sub-Loci with Distinct Phenotypes

PubMed Central

Zeumer, Leilani; Sang, Allison; Niu, Haitao; Morel, Laurence

2010-01-01

The NZM2410-derived Sle2 lupus susceptibility locus induces an abnormal B cell differentiation which most prominently leads to the expansion of autoreactive B1a cells. We have mapped the expansion of B1a cells to three Sle2 sub-loci, Sle2a, Sle2b, and Sle2c. Sle2 also enhances the breach of B cell tolerance to nuclear antigens in the 56R anti-DNA immunoglobulin transgenic (Tg) model. This study used the Sle2 sub-congenic strains to map the activation of 56R Tg B cells. Sle2c strongly sustained the breach of tolerance and the activation of anti-DNA B cells. The production of Tg-encoded anti-DNA antibodies was more modest in Sle2a expressing mice, but Sle2a was responsible for the recruitment for Tg B cells to the marginal zone, a phenotype that has been found for 56R Tg B cells in mice expressing the whole Sle2 interval. In addition, Sle2a promoted the production of endogenously encoded anti-DNA antibodies. Overall, this study showed that at least two Sle2 genes are involved in the activation of anti-DNA B cells, and excluded more than two-thirds of the Sle2 interval from contributing to this phenotype. This constitutes an important step toward the identification of novel genes that play a critical role in B cell tolerance. PMID:21270826

Efficacy and Tolerability of Pharmacotherapy Options for the Treatment of Irritability in Autistic Children

PubMed Central

Kirino, Eiji

2014-01-01

Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed. PMID:24932108

The retest reliability of the six-minute walk test in patients referred to a cardiac rehabilitation programme.

PubMed

Hanson, Lisa C; McBurney, Helen; Taylor, Nicholas F

2012-03-01

The purpose of this paper was to determine if the Six-minute Walk Test (6MWT) was a reliable exercise test for patients referred to cardiac rehabilitation when up to three tests were performed and to determine if test scores differed according to between-test time interval. Thirty adults aged 63 ± 7.9 years referred to cardiac rehabilitation participated in a repeated measures reliability trial. Participants completed three 6MWTs within a one-week period. Participants were randomly allocated to one of three groups: on the first day, Group A completed three walks, Group B completed two walks and Group C completed one walk. Relative reliability was expressed in a ratio (ICC(2,1) ), and absolute reliability was expressed in metres (95% confidence intervals) for group and individuals. The 6MWT demonstrated a high level of relative reliability (intraclass correlation coefficients [ICC] = 0.94) across the three walks. There was no statistically significant difference between the test scores of the three groups. However, there was an increase in distance walked from the first to the second to the third 6MWT. Absolute reliability indicated that a change of at least 44 m would be required to be interpreted as true change in a group, and at least 95 m to be interpreted as true change in an individual with 95% confidence. Three 6MWTs completed in relatively short timeframes were not sufficient for reliable results as there was an increase in the distance walked, and relatively large increases in distances would be required to be interpreted as change. It did not make any difference whether the tests were all completed on one day or over one week. This study highlighted problems that may arise when relying on reliability coefficients alone to interpret reliability. These results suggest that the 6MWT may not have sufficient reliability to be a suitable test to evaluate exercise tolerance in patients referred to cardiac rehabilitation. Copyright © 2011 John Wiley & Sons, Ltd.

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

PubMed

Bucaneve, Giampaolo; Micozzi, Alessandra; Menichetti, Francesco; Martino, Pietro; Dionisi, M Stella; Martinelli, Giovanni; Allione, Bernardino; D'Antonio, Domenico; Buelli, Maurizio; Nosari, A Maria; Cilloni, Daniela; Zuffa, Eliana; Cantaffa, Renato; Specchia, Giorgina; Amadori, Sergio; Fabbiano, Francesco; Deliliers, Giorgio Lambertenghi; Lauria, Francesco; Foà, Robin; Del Favero, Albano

2005-09-08

The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known. Copyright 2005 Massachusetts Medical Society.

Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥65 years) with type 2 diabetes

PubMed Central

Iqbal, Nayyar; Allen, Elsie; Öhman, Peter

2014-01-01

Background Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥65 years and <65 years. Methods Pooled adverse event data from three placebo-controlled trials of 76–206 weeks’ duration in older (≥65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test). Results A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥65 years) with saxagliptin and six (none aged ≥65 years) with placebo. Older patients rarely experienced symptomatic confirmed hypoglycemia (fingerstick glucose ≤50 mg/dL; saxagliptin, n=1; placebo, n=2). Conclusion Saxagliptin add-on therapy was generally well tolerated in older patients aged ≥65 years with type 2 diabetes mellitus, with a long-term safety profile similar to that of placebo. PMID:25214775

Long-term safety and tolerability of saxagliptin add-on therapy in older patients (aged ≥ 65 years) with type 2 diabetes.

PubMed

Iqbal, Nayyar; Allen, Elsie; Öhman, Peter

2014-01-01

Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥ 65 years and <65 years. Pooled adverse event data from three placebo-controlled trials of 76-206 weeks' duration in older (≥ 65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test). A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥ 65 years) with saxagliptin and six (none aged ≥ 65 years) with placebo. Older patients rarely experienced symptomatic confirmed hypoglycemia (fingerstick glucose ≤ 50 mg/dL; saxagliptin, n=1; placebo, n=2). Saxagliptin add-on therapy was generally well tolerated in older patients aged ≥ 65 years with type 2 diabetes mellitus, with a long-term safety profile similar to that of placebo.

Inheritance of mercury tolerance in the aquatic oligochaete Tubifex tubifex.

PubMed

Vidal, Dora Elva; Horne, Alex John

2003-09-01

Resistance to contaminants is an important yet unmeasured factor in sediment toxicity tests. The rate at which mercury resistance develops and its genetic persistence in the oligochaete worm Tubifex tubifex were studied under laboratory conditions. Worms were raised for four generations under two different sediment treatments, one reference clean sediment, the other contaminated with mercury. Worms raised in mercury-contaminated sediment developed mercury tolerance that persisted even when the worms were raised for three subsequent generations in clean sediment. Mercury tolerance was determined by comparative water-only toxicity tests with mercury as the only stressor. Control worms had a mean lethal concentration (LC50) of 0.18 mg/L(-1). Worms exposed to high levels of mercury in sediment had high mercury tolerance with a mean LC50 of 1.40 mg/L(-1). When mercury-tolerant and control mercury-intolerant worms were crossed, their descendants also demonstrated mercury tolerance during lethal toxicity tests. The LC50 for worm descendants resulting from this cross was 1.39 mg/L(-1). Adaptation to mercury exposures occurred rapidly in this group of worms and appears to be due to both phenotypic and genotypic mechanisms. Development of contaminant resistance and adaptation may be common phenomena in aquatic benthic invertebrates, which should be considered during the design and interpretation of toxicity tests.

Glucose Tolerance Testing and Anthropometric Comparisons Among Rural Residents of Kyiv Region: Investigating the Possible Effect of Childhood Starvation-A Community-Based Study.

PubMed

Khalangot, Mykola D; Kovtun, Volodymir A; Okhrimenko, Nadia V; Gurianov, Vitaly G; Kravchenko, Victor I

2017-01-01

A relationship between childhood starvation and type 2 diabetes mellitus (T2D) in adulthood was previously indicated. Ukraine suffered a series of artificial famines between 1921 and 1947. Famines of 1932 to 1933 and 1946 were most severe among them. Long-term health consequences of these famines remain insufficiently investigated. Type 2 diabetes mellitus screening was conducted between June 2013 and December 2014. A total of 198 rural residents of Kyiv region more than 44 years of age, not registered as patients with T2D, were randomly selected. In all, 159 persons answered the question about starvation of parental family, including 73 born before 1947. Among them, 62 persons answered positive. Anthropometric measurements and glucose tolerance tests were performed. A logistic regression model was used to evaluate results. Type 2 diabetes mellitus was detected in 7 of 62 persons (11.3%), who starved during childhood vs 6 of 11 (54.5%) who did not ( P  = .002), age-adjusted and sex-adjusted odds ratio (OR) (95% confidence interval): 0.063 (0.007-0.557). Analysis of the anthropometric data revealed a negative connection between adulthood height and neck circumference (cm, continued variables) and childhood starvation: age-adjusted and sex-adjusted ORs 0.86 (0.76-0.97) and 0.73 (0.54-0.97), respectively. Individuals who starved during famines of 1932 to 1933 and 1946 in Ukraine had a decreased T2D prevalence several decades after the famine episodes.

Glucose Tolerance Testing and Anthropometric Comparisons Among Rural Residents of Kyiv Region: Investigating the Possible Effect of Childhood Starvation—A Community-Based Study

PubMed Central

Khalangot, Mykola D; Kovtun, Volodymir A; Okhrimenko, Nadia V; Gurianov, Vitaly G; Kravchenko, Victor I

2017-01-01

A relationship between childhood starvation and type 2 diabetes mellitus (T2D) in adulthood was previously indicated. Ukraine suffered a series of artificial famines between 1921 and 1947. Famines of 1932 to 1933 and 1946 were most severe among them. Long-term health consequences of these famines remain insufficiently investigated. Type 2 diabetes mellitus screening was conducted between June 2013 and December 2014. A total of 198 rural residents of Kyiv region more than 44 years of age, not registered as patients with T2D, were randomly selected. In all, 159 persons answered the question about starvation of parental family, including 73 born before 1947. Among them, 62 persons answered positive. Anthropometric measurements and glucose tolerance tests were performed. A logistic regression model was used to evaluate results. Type 2 diabetes mellitus was detected in 7 of 62 persons (11.3%), who starved during childhood vs 6 of 11 (54.5%) who did not (P = .002), age-adjusted and sex-adjusted odds ratio (OR) (95% confidence interval): 0.063 (0.007-0.557). Analysis of the anthropometric data revealed a negative connection between adulthood height and neck circumference (cm, continued variables) and childhood starvation: age-adjusted and sex-adjusted ORs 0.86 (0.76-0.97) and 0.73 (0.54-0.97), respectively. Individuals who starved during famines of 1932 to 1933 and 1946 in Ukraine had a decreased T2D prevalence several decades after the famine episodes. PMID:29225471

Handling Ibuprofen Increases Pain Tolerance and Decreases Perceived Pain Intensity in a Cold Pressor Test

PubMed Central

Rutchick, Abraham M.; Slepian, Michael L.

2013-01-01

Pain contributes to health care costs, missed work and school, and lower quality of life. Extant research on psychological interventions for pain has focused primarily on developing skills that individuals can apply to manage their pain. Rather than examining internal factors that influence pain tolerance (e.g., pain management skills), the current work examines factors external to an individual that can increase pain tolerance. Specifically, the current study examined the nonconscious influence of exposure to meaningful objects on the perception of pain. Participants (N = 54) completed a cold pressor test, examined either ibuprofen or a control object, then completed another cold pressor test. In the second test, participants who previously examined ibuprofen reported experiencing less intense pain and tolerated immersion longer (relative to baseline) than those who examined the control object. Theoretical and applied implications of these findings are discussed. PMID:23469170

Exercise Intensity Thresholds: Identifying the Boundaries of Sustainable Performance.

PubMed

Keir, Daniel A; Fontana, Federico Y; Robertson, Taylor C; Murias, Juan M; Paterson, Donald H; Kowalchuk, John M; Pogliaghi, Silvia

2015-09-01

Critical power (CP), respiratory compensation point (RCP), maximal lactate steady state (MLSS), and deoxyhemoglobin breakpoint ([HHb]BP) are alternative functional indices that are thought to demarcate the highest exercise intensity that can be tolerated for long durations. We tested the hypothesis that CP, RCP, MLSS, and [HHb]BP occur at the same metabolic intensity by examining the pulmonary oxygen uptake (V˙)O2p and power output (PO) associated with each "threshold." Twelve healthy men (mean ± SD age, 27 ± 3 yr) performed the following tests on a cycle ergometer: i) four to five exhaustive tests for determination of CP, ii) two to three 30-min constant-power trials for MLSS determination, and iii) a ramp incremental exercise test from which the V˙O2p and PO at RCP and [HHb]BP were determined. During each trial, breath-by-breath V˙O2p and ventilatory variables were measured with a metabolic cart and flowmeter turbine; near-infrared spectroscopy-derived [HHb] was monitored using a frequency domain multidistance system, and arterialized capillary blood lactate was sampled at regular intervals. There were no differences (P > 0.05) among the V˙O2p values associated with CP, RCP, MLSS, and [HHb]BP (CP, 3.29 ± 0.48; RCP, 3.34 ± 0.45; MLSS, 3.27 ± 0.44; [HHb]BP, 3.41 ± 0.46 L·min(-1)); however, the PO associated with RCP (262 ± 48 W) and [HHb]BP (273 ± 41 W) were greater (P < 0.05) than both CP (226 ± 45 W) and MLSS (223 ± 39 W), which, themselves, were not different (P > 0.05). Although the standard methods for determination of CP, RCP, MLSS, and [HHb]BP are different, these indices occur at the same V˙O2p, suggesting that i) they may manifest as a result of similar physiological phenomenon and ii) each provides a valid delineation between tolerable and intolerable constant-power exercise.

Fasting Insulin is Better Partitioned according to Family History of Type 2 Diabetes Mellitus than Post Glucose Load Insulin of Oral Glucose Tolerance Test in Young Adults.

PubMed

Francis, Saritha; Chandran, Sindhu Padinjareveedu; Nesheera, K K; Jacob, Jose

2017-05-01

Hyperinsulinemia is contributed by insulin resistance, hepatic insulin uptake, insulin secretion and rate of insulin degradation. Family history of type 2 diabetes mellitus has been reported to cause hyperinsulinemia. Correlation of fasting insulin with post glucose load Oral Glucose Tolerance Test (OGTT) insulin in young adults and their partitioning according to family history of type 2 diabetes. In this observational cross-sectional study, clinical evaluation and biochemical assays of insulin and diabetes related parameters, and secondary clinical influences on type 2 diabetes in volunteers were done for inclusion as participants (n=90) or their exclusion. Cut off levels of quantitative biochemical variables were fixed such that they included the effects of insulin resistance, but excluded other secondary clinical influences. Distribution was analysed by Shapiro-Wilk test; equality of variances by Levene's test; Log 10 transformations for conversion of groups to Gaussian distribution and for equality of variances in the groups compared. When the groups compared had Gaussian distribution and there was equality of variance, parametric methods were used. Otherwise, non parametric methods were used. Fasting insulin was correlating significantly with 30, 60 and 120 minute OGTT insulin showing that hyperinsulinemia in the fasting state was related to hyperinsulinemia in the post glucose load states. When fasting and post glucose load OGTT insulin were partitioned into those without and with family history of type 2 diabetes, maximum difference was seen in fasting insulin (p<0.001), followed by 120 (p=0.001) and 60 (p= 0.002) minute OGTT insulin. The 30 minute insulin could not be partitioned (p=0.574). Fasting, 60 and 120 minute OGTT insulin can be partitioned according to family history of type 2 diabetes, demonstrating stratification and heterogeneity in the insulin sample. Of these, fasting insulin was better partitioned and could be used for baseline reference interval calculations.

Effects of treatment in women with gestational diabetes mellitus: systematic review and meta-analysis.

PubMed

Horvath, Karl; Koch, Klaus; Jeitler, Klaus; Matyas, Eva; Bender, Ralf; Bastian, Hilda; Lange, Stefan; Siebenhofer, Andrea

2010-04-01

To summarise the benefits and harms of treatments for women with gestational diabetes mellitus. Systematic review and meta-analysis of randomised controlled trials. Embase, Medline, AMED, BIOSIS, CCMed, CDMS, CDSR, CENTRAL, CINAHL, DARE, HTA, NHS EED, Heclinet, SciSearch, several publishers' databases, and reference lists of relevant secondary literature up to October 2009. Review methods Included studies were randomised controlled trials of specific treatment for gestational diabetes compared with usual care or "intensified" compared with "less intensified" specific treatment. Five randomised controlled trials matched the inclusion criteria for specific versus usual treatment. All studies used a two step approach with a 50 g glucose challenge test or screening for risk factors, or both, and a subsequent 75 g or 100 g oral glucose tolerance test. Meta-analyses did not show significant differences for most single end points judged to be of direct clinical importance. In women specifically treated for gestational diabetes, shoulder dystocia was significantly less common (odds ratio 0.40, 95% confidence interval 0.21 to 0.75), and one randomised controlled trial reported a significant reduction of pre-eclampsia (2.5 v 5.5%, P=0.02). For the surrogate end point of large for gestational age infants, the odds ratio was 0.48 (0.38 to 0.62). In the 13 randomised controlled trials of different intensities of specific treatments, meta-analysis showed a significant reduction of shoulder dystocia in women with more intensive treatment (0.31, 0.14 to 0.70). Treatment for gestational diabetes, consisting of treatment to lower blood glucose concentration alone or with special obstetric care, seems to lower the risk for some perinatal complications. Decisions regarding treatment should take into account that the evidence of benefit is derived from trials for which women were selected with a two step strategy (glucose challenge test/screening for risk factors and oral glucose tolerance test).

Specialized physiological studies in support of manned space flight

NASA Technical Reports Server (NTRS)

Luft, U. C.

1976-01-01

Subjects were tested for tolerance to lower body negative pressure (LBNP) before and after acute dehydration by working intermittenly for two hours without fluid replacement. On the second day there-after the LBNP tests were repeated before and after acute dehydration. The LBNP test consisted of 5 min long consective stages at -20, -30, -40, -50 and -60 Torr. Tests were terminated when syncope was imminent or the full sequence was completed. Tolerance was expressed in terms of cumulative stress in Torr x min. Measurements of body mass, density, fat fraction and total body water (TBW) were made before and after acclimation. Blood volume and its constituents were determined before and after each of the four LBNP tests. During LBNP, heart rate, blood pressure, and changes in calf and forearm volume were recorded every minute. Results showed: acute dehydration caused a significant loss in average LBNP tolerance on all subjects. Acclimation to heat did not significantly affect LBNP tolerance in hydrated subjects but significantly improved it on dehydrated subjects.

Perception of Community Tolerance and Prevalence of Depression among Transgender Persons.

PubMed

Owen-Smith, Ashli A; Sineath, Craig; Sanchez, Travis; Dea, Robin; Giammattei, Shawn; Gillespie, Theresa; Helms, Monica F; Hunkeler, Enid M; Quinn, Virginia P; Roblin, Douglas; Slovis, Jennifer; Stephenson, Robert; Sullivan, Patrick S; Tangpricha, Vin; Woodyatt, Cory; Goodman, Michael

2017-01-01

The goal of the study was to examine the association between depression and perceived community tolerance after controlling for various demographic and personal characteristics, treatment receipt, and past experiences with abuse or discrimination. An on-line survey assessed depressive symptoms among transgender and gender non-conforming individuals. Depression was assessed using the 7-item Beck Depression Inventory for Primary Care (BDI-PC) and the 10-item Center for Epidemiologic Studies Depression (CESD-10) scale. The prevalence ratios (95% confidence intervals) comparing depression in persons who did and did not perceive their area as tolerant were 0.33 (0.20-0.54) for BD-PC and 0.66 (0.49-0.89) for CESD-10. Other factors associated with depression were experience with abuse or discrimination, lower education, and unfulfilled desire to receive hormonal therapy. Depression was common in this sample of transgender and gender non-conforming individuals and was strongly and consistently associated with participants' perceptions of community tolerance, even after adjusting for possible confounding. The association between desire to receive hormonal therapy and depression is a finding that warrants further exploration. Future research should also assess depression and changes in perception of community tolerance in transgender individuals before and after initiation of gender confirmation treatment.

Effectiveness of Interval Exercise Training in Patients with COPD

PubMed Central

Kortianou, Eleni A.; Nasis, Ioannis G.; Spetsioti, Stavroula T.; Daskalakis, Andreas M.; Vogiatzis, Ioannis

2010-01-01

Physical training is beneficial and should be included in the comprehensive management of all patients with COPD independently of disease severity. Different rehabilitative strategies and training modalities have been proposed to optimize exercise tolerance. Interval exercise training has been used as an effective alternative modality to continuous exercise in patients with moderate and severe COPD. Although in healthy elderly individuals and patients with chronic heart failure there is evidence that this training modality is superior to continuous exercise in terms of physiological training effects, in patients with COPD, there is not such evidence. Nevertheless, in patients with COPD application of interval training has been shown to be equally effective to continuous exercise as it induces equivalent physiological training effects but with less symptoms of dyspnea and leg discomfort during training. The main purpose of this review is to summarize previous studies of the effectiveness of interval training in COPD and also to provide arguments in support of the application of interval training to overcome the respiratory and peripheral muscle limiting factors of exercise capacity. To this end we make recommendations on how best to implement interval training in the COPD population in the rehabilitation setting so as to maximize training effects. PMID:20957074

Application of damage tolerance methodology in certification of the Piaggio P-180 Avanti

NASA Technical Reports Server (NTRS)

Johnson, Jerry

1992-01-01

The Piaggio P-180 Avanti, a twin pusher-prop engine nine-passenger business aircraft was certified in 1990, to the requirements of FAR Part 23 and Associated Special Conditions for Composite Structure. Certification included the application of a damage tolerant methodology to the design of the composite forward wing and empennage (vertical fin, horizontal stabilizer, tailcone, and rudder) structure. This methodology included an extensive analytical evaluation coupled with sub-component and full-scale testing of the structure. The work from the Damage Tolerance Analysis Assessment was incorporated into the full-scale testing. Damage representing hazards such as dropped tools, ground equipment, handling, and runway debris, was applied to the test articles. Additional substantiation included allowing manufacturing discrepancies to exist unrepaired on the full-scale articles and simulated bondline failures in critical elements. The importance of full-scale testing in the critical environmental conditions and the application of critical damage are addressed. The implication of damage tolerance on static and fatigue testing is discussed. Good correlation between finite element solutions and experimental test data was observed.

Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans

PubMed Central

Sagoo, Pervinder; Perucha, Esperanza; Sawitzki, Birgit; Tomiuk, Stefan; Stephens, David A.; Miqueu, Patrick; Chapman, Stephanie; Craciun, Ligia; Sergeant, Ruhena; Brouard, Sophie; Rovis, Flavia; Jimenez, Elvira; Ballow, Amany; Giral, Magali; Rebollo-Mesa, Irene; Le Moine, Alain; Braudeau, Cecile; Hilton, Rachel; Gerstmayer, Bernhard; Bourcier, Katarzyna; Sharif, Adnan; Krajewska, Magdalena; Lord, Graham M.; Roberts, Ian; Goldman, Michel; Wood, Kathryn J.; Newell, Kenneth; Seyfert-Margolis, Vicki; Warrens, Anthony N.; Janssen, Uwe; Volk, Hans-Dieter; Soulillou, Jean-Paul; Hernandez-Fuentes, Maria P.; Lechler, Robert I.

2010-01-01

Identifying transplant recipients in whom immunological tolerance is established or is developing would allow an individually tailored approach to their posttransplantation management. In this study, we aimed to develop reliable and reproducible in vitro assays capable of detecting tolerance in renal transplant recipients. Several biomarkers and bioassays were screened on a training set that included 11 operationally tolerant renal transplant recipients, recipient groups following different immunosuppressive regimes, recipients undergoing chronic rejection, and healthy controls. Highly predictive assays were repeated on an independent test set that included 24 tolerant renal transplant recipients. Tolerant patients displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, a lack of donor-specific antibodies, donor-specific hyporesponsiveness of CD4+ T cells, and a high ratio of forkhead box P3 to α-1,2-mannosidase gene expression. Microarray analysis further revealed in tolerant recipients a bias toward differential expression of B cell–related genes and their associated molecular pathways. By combining these indices of tolerance as a cross-platform biomarker signature, we were able to identify tolerant recipients in both the training set and the test set. This study provides an immunological profile of the tolerant state that, with further validation, should inform and shape drug-weaning protocols in renal transplant recipients. PMID:20501943

Differential expression of benzodiazepine anticonvulsant cross-tolerance according to time following flurazepam or diazepam treatment.

PubMed

Rosenberg, H C

1995-01-01

In previous studies in which the anti-pentylenetetrazol (PTZ) effect of benzodiazepines was used to measure tolerance, the results depended on the benzodiazepine used for chronic treatment as well as the benzodiazepine given acutely to test for tolerance. In this study, the time course of tolerance reversal was studied in rats given two treatments known to cause anticonvulsant tolerance, 1-week flurazepam (FZP), and 3-week diazepam (DZP). Neither treatment altered convulsive threshold for IV PTZ, but both treatments decreased the convulsive threshold for bicuculline. Withdrawing DZP, but not FZP, treatment resulted in a loss of body weight. Twelve hours after 1-week FZP treatment, all benzodiazepines were significantly less effective, showing tolerance. Forty-eight hours after the 1-week FZP treatment, tolerance was still observed with DZP, FZP, and zolpidem, but was no longer present with clonazepam or bretazenil. After the 3-week DZP treatment, rats were tolerant to all benzodiazepines tested at 12 h of withdrawal, but had lost tolerance to all the drugs except bretazenil by 48 h. The results suggest differences in the way these benzodiazepines interact with their receptors, allowing differential expression of tolerance, and that chronic DZP and FZP treatments affected interactions of the benzodiazepines with their receptors, but not in the same fashion.

Effect of Surgical Curve Correction on Exercise Tolerance and Physical Capacities in Patients of Severe Spinal Deformity.

PubMed

Patil, Prateek C; Rathod, Ashok K; Borde, Mandar; Singh, Vishwajeet; Singh, Hemant U

2016-12-01

Traditionally, surgical intervention for patients with a spinal deformity has been considered for cosmetic benefits, but surgical intervention can alter the lung physiology or volumes and in turn leads to increase in physical capacity and exercise tolerance. Therefore, we conducted this to determine whether a surgical correction would restore the lung physiology, physical capacity and exercise tolerance in patients with kyphoscoliosis. To evaluate the usage of six-minute walk test scores and modified Borg scores as tools/measures for exercise tolerance in patients with spinal deformity and to study the effects of surgical correction of spinal deformity on exercise tolerance with above parameters as the measures. Thirty patients with spinal deformity, who had undergone surgery for deformity correction, were evaluated. All patients were investigated pre-operatively with x-rays of the spine (anteroposterior and lateral views). Clinical tests like breath holding time (after full inspiration) in number of seconds, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked); were recorded as measures of exercise tolerance. The patients were followed up on the first, third, sixth and twelfth month post-operatively and tested clinically for breath holding time, modified Borg scores, six-minute walk test scores (heart rate, respiratory rate, maximum distance walked) and x-rays of the spine (anteroposterior and lateral views). In our study, breath holding time (p-value = 0.001) and modified Borg scores (p-value = 0.012) showed a significant improvement at 12 months post-operatively. We noted similar findings with heart rate, respiratory rate and maximum distance walked after a six-minute walk test. Improvements were noted in all the parameters, especially in the group of patients with greater than 60 degrees of cobb angle. However, the differences between the two groups (pre-operative cobb angle less than 60 degrees and pre-operative cobb angle more than 60 degrees) were not significant. The results were analysed and tested for significance using Student's t-test (paired and unpaired as appropriate) and Wilcoxon signed rank test. Surgical correction in cases of spinal deformity improves the cosmetic appearance and balance in the patients. Favourable results of surgical intervention were found in exercise tolerance with improvements in modified Borg scores, six-minute walk test results and breath holding time. The above parameters appear to be good tools for the assessment of physical capacity and exercise tolerance in patients with spinal deformity.

Individual Differences in the Temporal Profile of Cardiovascular Responses to Head Down Tilt and Orthostatic Stress with and Without Fluid Loading

NASA Technical Reports Server (NTRS)

Cowings, Patricia; Toscano, William; Kanis, Dionisios; Gebreyesus, Fiyore

2013-01-01

Susceptibility of healthy astronauts to orthostatic hypotension and presyncope is exacerbated upon return from spaceflight. Hypo-volemia is suspected to play an important role in cardiovascular deconditioning following exposure to spaceflight, which may lead to increased peripheral resistance, attenuated arterial baroreflex, and changes in cardiac function. The effect of altered gravity during space flight and planetary transition on human cardiovascular function is of critical importance to maintenance of astronaut health and safety. A promising countermeasure for post-flight orthostatic intolerance is fluid loading used to restore loss fluid volume by giving crew salt tablets and water prior to re-entry. Eight men and eight women will be tested during two, 6-hour exposures to 6o HDT: 1) fluid loading, 2) no fluid loading. Before and immediately after each HDT, subjects will perform a stand test to assess their orthostatic tolerance. Physiological measures (e.g., ECG, blood pressure, peripheral blood volume) will be continuously monitored while echocardiography measures are recorded at 30-minute intervals during HDT and stand tests. Preliminary results (N=4) clearly show individual differences in responses to this countermeasure and the time course of physiological changes induced by HDT.

40 CFR Table E-2 to Subpart E of... - Spectral Energy Distribution and Permitted Tolerance for Conducting Radiative Tests

Code of Federal Regulations, 2010 CFR

2010-07-01

... Permitted Tolerance for Conducting Radiative Tests E Table E-2 to Subpart E of Part 53 Protection of... Reference Methods and Class I and Class II Equivalent Methods for PM2.5 or PM10â2.5 Pt. 53, Subpt. E, Table E-2 Table E-2 to Subpart E of Part 53—Spectral Energy Distribution and Permitted Tolerance for...

Noise-tolerant instantaneous heart rate and R-peak detection using short-term autocorrelation for wearable healthcare systems.

PubMed

Fujii, Takahide; Nakano, Masanao; Yamashita, Ken; Konishi, Toshihiro; Izumi, Shintaro; Kawaguchi, Hiroshi; Yoshimoto, Masahiko

2013-01-01

This paper describes a robust method of Instantaneous Heart Rate (IHR) and R-peak detection from noisy electrocardiogram (ECG) signals. Generally, the IHR is calculated from the R-wave interval. Then, the R-waves are extracted from the ECG using a threshold. However, in wearable bio-signal monitoring systems, noise increases the incidence of misdetection and false detection of R-peaks. To prevent incorrect detection, we introduce a short-term autocorrelation (STAC) technique and a small-window autocorrelation (SWAC) technique, which leverages the similarity of QRS complex waveforms. Simulation results show that the proposed method improves the noise tolerance of R-peak detection.

pH Tolerance in Freshwater Bacterioplankton: Trait Variation of the Community as Measured by Leucine Incorporation

PubMed Central

Kritzberg, Emma

2015-01-01

pH is an important factor determining bacterial community composition in soil and water. We have directly determined the community tolerance (trait variation) to pH in communities from 22 lakes and streams ranging in pH from 4 to 9 using a growth-based method not relying on distinguishing between individual populations. The pH in the water samples was altered to up to 16 pH values, covering in situ pH ± 2.5 U, and the tolerance was assessed by measuring bacterial growth (Leu incorporation) instantaneously after pH adjustment. The resulting unimodal response curves, reflecting community tolerance to pH, were well modeled with a double logistic equation (mean R2 = 0.97). The optimal pH for growth (pHopt) among the bacterial communities was closely correlated with in situ pH, with a slope (0.89 ± 0.099) close to unity. The pH interval, in which growth was ≥90% of that at pHopt, was 1.1 to 3 pH units wide (mean 2.0 pH units). Tolerance response curves of communities originating from circum-neutral pH were symmetrical, whereas in high-pH (8.9) and especially in low-pH (<5.5) waters, asymmetric tolerance curves were found. In low-pH waters, decreasing pH was more detrimental for bacterial growth than increasing pH, with a tendency for the opposite for high-pH waters. A pH tolerance index, using the ratio of growth at only two pH values (pH 4 and 8), was closely related to pHopt (R2 = 0.83), allowing for easy determination of pH tolerance during rapid changes in pH. PMID:26276108

Six-minute-walk distance and accelerometry predict outcomes in chronic obstructive pulmonary disease independent of Global Initiative for Chronic Obstructive Lung Disease 2011 Group.

PubMed

Durheim, Michael T; Smith, Patrick J; Babyak, Michael A; Mabe, Stephanie K; Martinu, Tereza; Welty-Wolf, Karen E; Emery, Charles F; Palmer, Scott M; Blumenthal, James A

2015-03-01

The 2011 combined Global Initiative for Chronic Obstructive Lung Disease (GOLD) assessment incorporates symptoms, exacerbation history, and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). Six-minute-walk distance (6MWD) and accelerometry also have been used to assess disease severity in COPD. The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown. To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD-related hospitalization or all-cause mortality, independent of GOLD 2011 group. Physical function and medical outcomes were prospectively assessed in 326 patients with moderate to severe COPD in INSPIRE-II, a randomized controlled trial of a coping skills training intervention. Cox models were used to determine if GOLD 2011 group, 6MWD, or accelerometry steps were associated with risk of COPD-related hospitalization or all-cause mortality. Physical function declined over time in GOLD group D but remained stable in groups A, B, and C. GOLD classification was associated with time to death or first COPD-related hospitalization. Baseline 6MWD was more strongly associated with time to death or first COPD-related hospitalization (hazard ratio, 0.50 [95% confidence interval, 0.34, 0.73] per 150 m, P=0.0003) than GOLD 2011 classification. A similar relationship was observed for accelerometry steps (hazard ratio, 0.80 [95% confidence interval, 0.70, 0.92] per 1,000 steps, P=0.002). Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD, independent of GOLD 2011 classification. Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinically meaningful outcomes in COPD.

Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

PubMed

Gisbert, Javier P; Pérez-Aisa, Angeles; Bermejo, Fernando; Castro-Fernández, Manuel; Almela, Pedro; Barrio, Jesús; Cosme, Angel; Modolell, Inés; Bory, Felipe; Fernández-Bermejo, Miguel; Rodrigo, Luis; Ortuño, Jesús; Sánchez-Pobre, Pilar; Khorrami, Sam; Franco, Alejandro; Tomas, Albert; Guerra, Iván; Lamas, Eloisa; Ponce, Julio; Calvet, Xavier

2013-02-01

Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Prospective multicenter study. In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

Where does HIT fit? An examination of the affective response to high-intensity intervals in comparison to continuous moderate- and continuous vigorous-intensity exercise in the exercise intensity-affect continuum.

PubMed

Jung, Mary E; Bourne, Jessica E; Little, Jonathan P

2014-01-01

Affect experienced during an exercise session is purported to predict future exercise behaviour. Compared to continuous moderate-intensity exercise (CMI), the affective response to continuous vigorous-intensity exercise (CVI) has consistently been shown to be more aversive. The affective response, and overall tolerability to high-intensity interval training (HIT), is less studied. To date, there has yet to be a comparison between HIT, CVI, and CMI. The purpose of this study was to compare the tolerability and affective responses during HIT to CVI and CMI. This study utilized a repeated measures, randomized, counter-balanced design. Forty-four participants visited the laboratory on four occasions. Baseline fitness testing was conducted to establish peak power output in Watts (W peak). Three subsequent visits involved a single bout of a) HIT, corresponding to 1-minute at ∼ 100% W peak and 1-minute at ∼ 20% W peak for 20 minutes, b) CMI, corresponding to ∼ 40% W peak for 40 minutes, and c) CVI, corresponding to ∼ 80% W peak for 20 minutes. The order of the sessions was randomized. Affective responses were measured before, during and after each session. Task self-efficacy, intentions, enjoyment and preference were measured after sessions. Participants reported greater enjoyment of HIT as compared to CMI and CVI, with over 50% of participants reporting a preference to engage in HIT as opposed to either CMI or CVI. HIT was considered more pleasurable than CVI after exercise, but less pleasurable than CMI at these times. Despite this participants reported being just as confident to engage in HIT as they were CMI, but less confident to engage in CVI. This study highlights the utility of HIT in inactive individuals, and suggests that it may be a viable alternative to traditionally prescribed continuous modalities of exercise for promoting self-efficacy and enjoyment of exercise.

Where Does HIT Fit? An Examination of the Affective Response to High-Intensity Intervals in Comparison to Continuous Moderate- and Continuous Vigorous-Intensity Exercise in the Exercise Intensity-Affect Continuum

PubMed Central

Jung, Mary E.; Bourne, Jessica E.; Little, Jonathan P.

2014-01-01

Affect experienced during an exercise session is purported to predict future exercise behaviour. Compared to continuous moderate-intensity exercise (CMI), the affective response to continuous vigorous-intensity exercise (CVI) has consistently been shown to be more aversive. The affective response, and overall tolerability to high-intensity interval training (HIT), is less studied. To date, there has yet to be a comparison between HIT, CVI, and CMI. The purpose of this study was to compare the tolerability and affective responses during HIT to CVI and CMI. This study utilized a repeated measures, randomized, counter-balanced design. Forty-four participants visited the laboratory on four occasions. Baseline fitness testing was conducted to establish peak power output in Watts (Wpeak). Three subsequent visits involved a single bout of a) HIT, corresponding to 1-minute at ∼100% Wpeak and 1-minute at ∼20% Wpeak for 20 minutes, b) CMI, corresponding to ∼40% Wpeak for 40 minutes, and c) CVI, corresponding to ∼80% Wpeak for 20 minutes. The order of the sessions was randomized. Affective responses were measured before, during and after each session. Task self-efficacy, intentions, enjoyment and preference were measured after sessions. Participants reported greater enjoyment of HIT as compared to CMI and CVI, with over 50% of participants reporting a preference to engage in HIT as opposed to either CMI or CVI. HIT was considered more pleasurable than CVI after exercise, but less pleasurable than CMI at these times. Despite this participants reported being just as confident to engage in HIT as they were CMI, but less confident to engage in CVI. This study highlights the utility of HIT in inactive individuals, and suggests that it may be a viable alternative to traditionally prescribed continuous modalities of exercise for promoting self-efficacy and enjoyment of exercise. PMID:25486273

Methamphetamine-Induced Locomotor Changes are Dependent on Age, Dose and Genotype

PubMed Central

Good, Renee L.; Radcliffe, Richard A.

2012-01-01

Adolescence is a critical age for addiction formation as a large percentage of pathological drug-seeking behaviors manifest during this time. The extent to which neurotoxic effects of drugs of abuse influence subsequent drug seeking behaviors and impulsivity is an understudied area of research. Methamphetamine (METH) is a widely abused drug that produces locomotor responses ranging from behavioral sensitization to tolerance, both of which are behaviors that may relate to risk of abuse. Here we investigated the effects of age, genotype, METH dose, including a neurotoxic dose, and METH metabolism on open-field activity (OFA) to gain insight into the complex disease of drug abuse. C57Bl/6 (B6), DBA/2 (D2), and 129S6SvEv/Tac (129) mouse strains were administered saline or either a high dose (4 × 5 mg/kg in 2h intervals for 2 days) or low dose (2 × 1 mg/kg in 24h intervals) METH pretreatment during adolescence (post natal day (PND) 40) or early adulthood (PND 80) followed by behavioral testing with a METH (1 mg/kg) or saline challenge 40 days later. Striatal concentrations of METH and AMPH were also determined. Significant findings include: 1) METH pretreated adolescent B6 mice displayed significant sensitization for horizontal locomotion due to high dose METH pretreatment; 2) METH pretreated B6 adults showed significant tolerance for the vertical activity measure caused by low dose METH pretreatment; 3) METH pretreated adult D2 mice exhibited significant sensitization for vertical activity induced by low dose METH pretreatment, and 4) 129 mice metabolized METH significantly faster than the B6 and D2 mice, but METH pretreatment did not alter metabolism. No significant behavioral responses to either METH pretreatment dose were observed for the D2 adolescent studies or either 129 age group. Our results highlight the importance of the interactions of age, strain and METH dose on locomotor behavioral outcomes. PMID:21163294

Fault tolerant control based on interval type-2 fuzzy sliding mode controller for coaxial trirotor aircraft.

PubMed

Zeghlache, Samir; Kara, Kamel; Saigaa, Djamel

2015-11-01

In this paper, a robust controller for a Six Degrees of Freedom (6 DOF) coaxial trirotor helicopter control is proposed in presence of defects in the system. A control strategy based on the coupling of the interval type-2 fuzzy logic control and sliding mode control technique are used to design a controller. The main purpose of this work is to eliminate the chattering phenomenon and guaranteeing the stability and the robustness of the system. In order to achieve this goal, interval type-2 fuzzy logic control has been used to generate the discontinuous control signal. The simulation results have shown that the proposed control strategy can greatly alleviate the chattering effect, and perform good reference tracking in presence of defects in the system. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

A simple approach to detect and correct signal faults of Hall position sensors for brushless DC motors at steady speed

NASA Astrophysics Data System (ADS)

Shi, Yongli; Wu, Zhong; Zhi, Kangyi; Xiong, Jun

2018-03-01

In order to realize reliable commutation of brushless DC motors (BLDCMs), a simple approach is proposed to detect and correct signal faults of Hall position sensors in this paper. First, the time instant of the next jumping edge for Hall signals is predicted by using prior information of pulse intervals in the last electrical period. Considering the possible errors between the predicted instant and the real one, a confidence interval is set by using the predicted value and a suitable tolerance for the next pulse edge. According to the relationship between the real pulse edge and the confidence interval, Hall signals can be judged and the signal faults can be corrected. Experimental results of a BLDCM at steady speed demonstrate the effectiveness of the approach.

Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years.

PubMed

Schmader, Kenneth E; Levin, Myron J; Gnann, John W; McNeil, Shelly A; Vesikari, Timo; Betts, Robert F; Keay, Susan; Stek, Jon E; Bundick, Nickoya D; Su, Shu-Chih; Zhao, Yanli; Li, Xiaoming; Chan, Ivan S F; Annunziato, Paula W; Parrino, Janie

2012-04-01

Herpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. In subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated. NCT00534248.

Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials

PubMed Central

Gauthier, Serge; Schlaefke, Sandra

2014-01-01

The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761® in dementia. Seven of 15 randomized, placebocontrolled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22–26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (−0.52; 95% confidence interval [CI] −0.98, −0.05; P=0.03), activities of daily living (−0.44; 95% CI −0.68, −0.19; P<0.001), and global rating (−0.52; 95% CI −0.92, −0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia. PMID:25506211

The Effects of Promethazine on Human Performance, Mood States, and Motion Sickness Tolerance

NASA Technical Reports Server (NTRS)

Cowings, Patricia S.; Stout, Cynthia; Toscano, William B.; Reynoso, Samuel; DeRoshia, Charles

1996-01-01

Intramuscular (IM) injections of promethazine in 25 mg or 50 mg dosages are commonly used to treat space motion sickness in astronauts. The present study examined the effects of IM injections of promethazine on neuropsy-chological performance, mood states, and motion sickness tolerance in humans. Twelve men, mean age 36 plus or minus 3.1 participated in one training (no injections) and three treatment conditions: a 25 mg injection of promethazine, a 50 mg injection of promethazine, and a placebo injection of sterile saline. Each condition, spaced at 7 day intervals, required an 8-10 hr session in which subjects were given four repetitions of 12 performance tasks, and one rotating chair motion sickness test. On the training day subjects were trained on each task to establish stability and proficiency. On treatment days, the order in which the drug or placebo was assigned to subjects was counter-balanced and a double-blind technique was used. Statistically significant decrements in performance were observed on 10 of 12 tasks when subjects were given 25 mg or 50 mg of promethazine as compared to the placebo. Performance decrements were associated with mean blood alcohol dose equivalency levels of 0.085% for 25 mg and 0. 1 37% for 50 mg dosages. The mood scale results showed significant changes in individual subjective experiences with maximum deterioration in the arousal state and fatigue level. When compared to placebo significant increases in motion sickness tolerance were found for both dosages of promethazine. These data suggest that effective dosages of promethazine currently used to counteract motion sickness in astronauts may significantly impair task components of their operational performance.

Analysis of platinum content in biodegradable carboplatin-impregnated beads and retrospective assessment of tolerability for intralesional use of the beads in dogs following excision of subcutaneous sarcomas: 29 cases (2011-2014).

PubMed

Hess, Theresa A; Drinkhouse, Macy E; Prey, Joshua D; Miller, Jonathan M; Fettig, Arthur A; Carberry, Carol A; Brenn, Stephen H; Bailey, Dennis B

2018-02-15

OBJECTIVE To evaluate platinum content in biodegradable carboplatin-impregnated beads and retrospectively assess tolerability and outcome data for dogs treated by intralesional placement of such beads following surgical excision of subcutaneous sarcomas. DESIGN Evaluation study and retrospective case series. SAMPLE 9 carboplatin-impregnated beads and 29 client-owned dogs. PROCEDURES Platinum content in 9 carboplatin-impregnated beads from 3 lots was measured by spectrophotometry, and calculated carboplatin content was compared with the labeled content. Medical records were searched to identify dogs with subcutaneous sarcomas for which treatment included placement of carboplatin-impregnated beads between 2011 and 2014. Signalment, tumor characteristics, surgical and histologic data, adverse events, and local recurrences were recorded. Associations between variables of interest and adverse events or local disease-free interval were analyzed. RESULTS In vitro analysis identified a mean ± SD platinum content of 5.38 ± 0.97 mg/bead. Calculated carboplatin content (10.24 ± 1.84 mg/bead) was significantly greater than the labeled amount (4.6 mg/bead). Bead weight and total platinum content differed significantly among lots, but platinum content per bead weight did not. Mild-to-moderate local adverse events were reported for 11 of 29 tumors; all resolved without additional surgery. No dogs had signs of systemic toxicosis. Overall local disease-free rates 1, 2, and 3 years after surgery were 70%, 70%, and 58%, respectively, as determined by Kaplan-Meier analysis. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated beads were well tolerated; however, results of in vitro tests indicated that caution is needed because of manufacturing inconsistencies.

Shuttle walking test and 6-minute walking test induce a similar cardiorespiratory performance in patients recovering from an acute exacerbation of chronic obstructive pulmonary disease.

PubMed

Vagaggini, B; Taccola, M; Severino, S; Marcello, M; Antonelli, S; Brogi, S; De Simone, C; Giardina, A; Paggiaro, P L

2003-01-01

The incremental shuttle walking test (SWT) has recently been proposed as a more valid and reproducible alternative to the conventional 6-min walking test (6MWT) in the evaluation of exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). To compare the cardiorespiratory performance obtained during two sessions of SWT with that obtained during two sessions of 6MWT. We examined 18 patients (forced expiratory volume in 1 s: 48 +/- 14%) recovering from an acute exacerbation of COPD that had required hospitalization. In the same afternoon, each patient performed two SWT and two 6MWT, with an interval of at least 30 min between each test; the sequence of the tests was randomized. Mean walking distance was greater in the second SWT test than in the first SWT. The changes from baseline in systolic blood pressure, heart rate, respiratory rate, oxygen saturation and dyspnea Borg index at the end of the test were similar between the two 6MWT and the two SWT. There was a highly significant correlation between walking distances measured during SWT and during 6MWT (rho: 0.85, p < 0.0005). Neither SWT nor 6MWT correlated with functional data of COPD. SWT, though being considered to be closer to a submaximal exercise test than 6MWT, does not induce a greater cardiorespiratory performance than 6MWT in patients recovering from acute exacerbation of COPD. Copyright 2003 S. Karger AG, Basel

Validation of a method for the quantitation of ghrelin and unacylated ghrelin by HPLC.

PubMed

Staes, Edith; Rozet, Eric; Ucakar, Bernard; Hubert, Philippe; Préat, Véronique

2010-02-05

An HPLC/UV method was first optimized for the separation and quantitation of human acylated and unacylated (or des-acyl) ghrelin from aqueous solutions. This method was validated by an original approach using accuracy profiles based on tolerance intervals for the total error measurement. The concentration range that achieved adequate accuracy extended from 1.85 to 59.30microM and 1.93 to 61.60microM for acylated and unacylated ghrelin, respectively. Then, optimal temperature, pH and buffer for sample storage were determined. Unacylated ghrelin was found to be stable in all conditions tested. At 37 degrees C acylated ghrelin was stable at pH 4 but unstable at pH 7.4, the main degradation product was unacylated ghrelin. Finally, this validated HPLC/UV method was used to evaluate the binding of acylated and unacylated ghrelin to liposomes.

Comparison of liquid chromatographic and bioassay procedures for determining depletion of intramuscularly injected tylosin.

PubMed

Moats, W A; Harris, E W; Steele, N C

1985-01-01

Crossbred pigs weighing 80-110 kg were injected intramuscularly in the ham with 8.8 mg/kg tylosin. Animals were slaughtered in groups of 3 at intervals of 4 h, and 1, 2, 4, and 8 days after injection, and samples of blood, injected muscle, uninjected muscle, liver, and kidney were analyzed by liquid chromatography (LC) and by bioassay using Sarcina lutea as the test organism. The LC method was far more sensitive with a detection limit of less than 0.1 ppm, while the detection limit by bioassay was about 0.5 ppm in tissue. Results by bioassay and LC sometimes differed considerably for tissue samples. Residues in all tissues were below the tolerance limit of 0.2 ppm at 24 h, except in the injected muscle in one animal. Residues were not detected in any tissue of any animal at 48 h after treatment.

Tolerance and UQ4SIM: Nimble Uncertainty Documentation and Analysis Software

NASA Technical Reports Server (NTRS)

Kleb, Bil

2008-01-01

Ultimately, scientific numerical models need quantified output uncertainties so that modeling can evolve to better match reality. Documenting model input uncertainties and variabilities is a necessary first step toward that goal. Without known input parameter uncertainties, model sensitivities are all one can determine, and without code verification, output uncertainties are simply not reliable. The basic premise of uncertainty markup is to craft a tolerance and tagging mini-language that offers a natural, unobtrusive presentation and does not depend on parsing each type of input file format. Each file is marked up with tolerances and optionally, associated tags that serve to label the parameters and their uncertainties. The evolution of such a language, often called a Domain Specific Language or DSL, is given in [1], but in final form it parallels tolerances specified on an engineering drawing, e.g., 1 +/- 0.5, 5 +/- 10%, 2 +/- 10 where % signifies percent and o signifies order of magnitude. Tags, necessary for error propagation, can be added by placing a quotation-mark-delimited tag after the tolerance, e.g., 0.7 +/- 20% 'T_effective'. In addition, tolerances might have different underlying distributions, e.g., Uniform, Normal, or Triangular, or the tolerances may merely be intervals due to lack of knowledge (uncertainty). Finally, to address pragmatic considerations such as older models that require specific number-field formats, C-style format specifiers can be appended to the tolerance like so, 1.35 +/- 10U_3.2f. As an example of use, consider figure 1, where a chemical reaction input file is has been marked up to include tolerances and tags per table 1. Not only does the technique provide a natural method of specifying tolerances, but it also servers as in situ documentation of model uncertainties. This tolerance language comes with a utility to strip the tolerances (and tags), to provide a path to the nominal model parameter file. And, as shown in [1], having the ability to quickly mark and identify model parameter uncertainties facilitates error propagation, which in turn yield output uncertainties.

Relationship between fish size and upper thermal tolerance

USGS Publications Warehouse

Recsetar, Matthew S.; Zeigler, Matthew P.; Ward, David L.; Bonar, Scott A.; Caldwell, Colleen A.

2012-01-01

Using critical thermal maximum (CTMax) tests, we examined the relationship between upper temperature tolerances and fish size (fry-adult or subadult lengths) of rainbow trout Oncorhynchus mykiss (41-200-mm TL), Apache trout O. gilae apache (40-220-mm TL), largemouth bass Micropterus salmoides (72-266-mm TL), Nile tilapia Oreochromis niloticus (35-206-mm TL), channel catfish Ictalurus punctatus (62-264 mm-TL), and Rio Grande cutthroat trout O. clarkii virginalis (36-181-mm TL). Rainbow trout and Apache trout were acclimated at 18°C, Rio Grande cutthroat trout were acclimated at 14°C, and Nile tilapia, largemouth bass, and channel catfish were acclimated at 25°C, all for 14 d. Critical thermal maximum temperatures were estimated and data were analyzed using simple linear regression. There was no significant relationship (P > 0.05) between thermal tolerance and length for Nile tilapia (P = 0.33), channel catfish (P = 0.55), rainbow trout (P = 0.76), or largemouth bass (P = 0.93) for the length ranges we tested. There was a significant negative relationship between thermal tolerance and length for Rio Grande cutthroat trout (R2 = 0.412, P 2 = 0.1374, P = 0.028); however, the difference was less than 1°C across all lengths of Apache trout tested and about 1.3°C across all lengths of Rio Grande cutthroat trout tested. Because there was either no or at most a slight relationship between upper thermal tolerance and size, management and research decisions based on upper thermal tolerance should be similar for the range of sizes within each species we tested. However, the different sizes we tested only encompassed life stages ranging from fry to adult/subadult, so thermal tolerance of eggs, alevins, and larger adults should also be considered before making management decisions affecting an entire species.

Design, testing, and damage tolerance study of bonded stiffened composite wing cover panels

NASA Technical Reports Server (NTRS)

Madan, Ram C.; Sutton, Jason O.

1988-01-01

Results are presented from the application of damage tolerance criteria for composite panels to multistringer composite wing cover panels developed under NASA's Composite Transport Wing Technology Development contract. This conceptual wing design integrated aeroelastic stiffness constraints with an enhanced damage tolerance material system, in order to yield optimized producibility and structural performance. Damage tolerance was demonstrated in a test program using full-sized cover panel subcomponents; panel skins were impacted at midbay between stiffeners, directly over a stiffener, and over the stiffener flange edge. None of the impacts produced visible damage. NASTRAN analyses were performed to simulate NDI-detected invisible damage.

A whole-plant screening test to identify genotypes with superior freezing tolerance.

PubMed

Bertrand, Annick; Castonguay, Yves; Bourassa, Josée

2014-01-01

Freezing tolerance is a determinant factor of persistence of perennials grown in northern climate. Selection for winterhardiness in field nurseries is difficult because of the unpredictability of occurrence of test winters allowing the identification of hardy genotypes. Here we describe a whole-plant assay entirely performed indoor in growth chambers and walk-in freezers to identify genotypes with superior tolerance to freezing within populations of open pollinated species. Three successive freezing stresses are applied to progressively eliminate 90 % of the population and to retain only the 10 % best performing genotypes. This approach can be used to generate recurrently selected populations more tolerant to freezing in different species.

Polycaprolactone/glass bioabsorbable implant in a rabbit humerus fracture model.

PubMed

Lowry, K J; Hamson, K R; Bear, L; Peng, Y B; Calaluce, R; Evans, M L; Anglen, J O; Allen, W C

1997-09-15

Research in improved materials and methods for internal fixation has centered on internal fixators made of bioabsorbable materials such as polylactic acid, polyglycolic acid, and polyparadioxanone. These materials have two problems: the first is a postoperative complication related to a delayed inflammatory response; and the second is low strength characteristics. An alternative material developed to alleviate these problems is a composite of phosphate glass fibers embedded in the polymer polycaprolactone, referred to as PCL. In this study, intramedullary pins made of PCL were compared to stainless steel pins in a rabbit humerus osteotomy model. Specimens were harvested at 0, 6, and 12 weeks postoperatively, radiographs and mechanical testing to failure were performed at each time interval, and tissue was examined microscopically at 6 and 12 weeks. Histologic results showed PCL pins to be well tolerated with minimal inflammation around the pin. Mechanical testing revealed the PCL fixation to be weaker initially than the stainless steel fixation. There was significant stress shielding of stainless-steel-healed rabbit humeri when compared to the PCL/bone humeri. All osteotomies immobilized with PCL healed with abundant periosteal callus production.

Consumption of açai (Euterpe oleracea Mart.) functional beverage reduces muscle stress and improves effort tolerance in elite athletes: a randomized controlled intervention study.

PubMed

Carvalho-Peixoto, Jacqueline; Moura, Mirian Ribeiro Leite; Cunha, Felipe Amorim; Lollo, Pablo Christiano B; Monteiro, Walace David; Carvalho, Lucia Maria Jaeger de; Farinatti, Paulo de Tarso Veras

2015-07-01

The study analyzed the effect of an açai (Euterpe oleracea Mart.) functional beverage (AB) on muscle and oxidative stress markers, cardiorespiratory responses, perceived exertion, and time-to-exhaustion during maximal treadmill running. The beverage was developed as an ergogenic aid for athletes and contained 27.6 mg of anthocyanins per dose. Fourteen athletes performed 3 exercise tests: a ramp-incremental maximal exercise test and 2 maximal exercise bouts performed in 2 conditions (AB and without AB (control)) at 90% maximal oxygen uptake. Blood was collected at baseline and after maximal exercise in both conditions to determine biomarkers. AB increased time to exhaustion during short-term high-intensity exercise (mean difference: 69 s, 95% confidence interval = -296 s to 159 s, t = 2.2, p = 0.045), attenuating the metabolic stress induced by exercise (p < 0.05). AB also reduced perceived exertion and enhanced cardiorespiratory responses (p < 0.05). The AB may be a useful and practical ergogenic aid to enhance performance during high-intensity training.

Pharmacokinetic Interactions between the Hormonal Emergency Contraception, Levonorgestrel (Plan B), and Efavirenz

PubMed Central

Carten, Monica L.; Kiser, Jennifer J.; Kwara, Awewura; Mawhinney, Samantha; Cu-Uvin, Susan

2012-01-01

Objectives. Compare the Plan B levonorgestrel (LNG) area under the concentration- time curve (AUC12) prior to and with efavirenz (EFV). Design. Prospective, open-label, single-arm, equivalence study. Methods. Healthy HIV-negative subjects underwent 12 hr intensive pharmacokinetic (PK) sampling following single dose LNG alone and after 14 days of EFV. Geometric means, Geometric Mean Ratios, and 90% confidence intervals (CI) are reported for PK Parameters. T-tests were utilized. Clinical parameters and liver function tests (LFTs) were assessed. Results. 24 women enrolled and 21 completed the study. With EFV, LNG AUC12 was reduced 56% (95% CI: 49%, 62%) from 42.9 to 17.8 ng∗hr/mL, and maximum concentration (Cmax⁡) was reduced 41% (95% CI: 33%, 50%) from 8.4 to 4.6 ng/mL. LNG was well tolerated with no grade 3 or 4 treatment-related toxicities. Conclusions. EFV significantly reduced LNG exposures. Higher LNG doses may be required with EFV. These results reinforce the importance of effective contraception in women taking EFV. PMID:22536010

The organization of irrational beliefs in posttraumatic stress symptomology: testing the predictions of REBT theory using structural equation modelling.

PubMed

Hyland, Philip; Shevlin, Mark; Adamson, Gary; Boduszek, Daniel

2014-01-01

This study directly tests a central prediction of rational emotive behaviour therapy (REBT) that has received little empirical attention regarding the core and intermediate beliefs in the development of posttraumatic stress symptoms. A theoretically consistent REBT model of posttraumatic stress disorder (PTSD) was examined using structural equation modelling techniques among a sample of 313 trauma-exposed military and law enforcement personnel. The REBT model of PTSD provided a good fit of the data, χ(2) = 599.173, df = 356, p < .001; standardized root mean square residual = .05 (confidence interval = .04-.05); standardized root mean square residual = .04; comparative fit index = .95; Tucker Lewis index = .95. Results demonstrated that demandingness beliefs indirectly affected the various symptom groups of PTSD through a set of secondary irrational beliefs that include catastrophizing, low frustration tolerance, and depreciation beliefs. Results were consistent with the predictions of REBT theory and provides strong empirical support that the cognitive variables described by REBT theory are critical cognitive constructs in the prediction of PTSD symptomology. © 2013 Wiley Periodicals, Inc.

Damage Tolerance of Composites

NASA Technical Reports Server (NTRS)

Hodge, Andy

2007-01-01

Fracture control requirements have been developed to address damage tolerance of composites for manned space flight hardware. The requirements provide the framework for critical and noncritical hardware assessment and testing. The need for damage threat assessments, impact damage protection plans, and nondestructive evaluation are also addressed. Hardware intended to be damage tolerant have extensive coupon, sub-element, and full-scale testing requirements in-line with the Building Block Approach concept from the MIL-HDBK-17, Department of Defense Composite Materials Handbook.

A randomised, double-blind, placebo-controlled, crossover study to assess the efficacy and safety of three dosing schedules of agalsidase alfa enzyme replacement therapy for Fabry disease.

PubMed

Hughes, D A; Deegan, P B; Milligan, A; Wright, N; Butler, L H; Jacobs, A; Mehta, A B

2013-07-01

Anecdotal reports suggest that the currently approved dosing interval of agalsidase alfa (0.2 mg/kg/2 weeks) for Fabry disease treatment is too long. This randomised, double-blind, placebo-controlled, crossover study investigated three altered dosing intervals. 18 Fabry patients received three agalsidase alfa dosing schedules, each for four weeks (A: 0.2 mg/kg∗2 weeks, B: 0.1 mg/kg/week, C: 0.2 mg/kg/week). Health state, pain levels, sweat volume and latency and plasma and urinary globotriaosylceramide levels were recorded throughout the study. No significant differences were found among the schedules for the primary efficacy outcome of self-assessed health state, or for pain scores. A trend toward increased sweat volume on QSART testing, and reduced urine globotriaosylceramide concentration were seen with treatment schedule C. Agalsidase alfa was safe and well tolerated with all schedules. In conclusion, the primary analyses did not find weekly infusions of agalsidase alfa to be statistically better than the approved dosing schedule however the data indicates that further studies with more patients over a longer period are required to more accurately determine the optimum dose and schedule. Copyright © 2013 Elsevier Inc. All rights reserved.

The Xenon Test Chamber Q-SUN® for testing realistic tolerances of fungi exposed to simulated full spectrum solar radiation.

PubMed

Dias, Luciana P; Araújo, Claudinéia A S; Pupin, Breno; Ferreira, Paulo C; Braga, Gilberto Ú L; Rangel, Drauzio E N

2018-06-01

The low survival of insect-pathogenic fungi when used for insect control in agriculture is mainly due to the deleterious effects of ultraviolet radiation and heat from solar irradiation. In this study, conidia of 15 species of entomopathogenic fungi were exposed to simulated full-spectrum solar radiation emitted by a Xenon Test Chamber Q-SUN XE-3-HC 340S (Q-LAB ® Corporation, Westlake, OH, USA), which very closely simulates full-spectrum solar radiation. A dendrogram obtained from cluster analyses, based on lethal time 50 % and 90 % calculated by Probit analyses, separated the fungi into three clusters: cluster 3 contains species with highest tolerance to simulated full-spectrum solar radiation, included Metarhizium acridum, Cladosporium herbarum, and Trichothecium roseum with LT 50  > 200 min irradiation. Cluster 2 contains eight species with moderate UV tolerance: Aschersonia aleyrodis, Isaria fumosorosea, Mariannaea pruinosa, Metarhizium anisopliae, Metarhizium brunneum, Metarhizium robertsii, Simplicillium lanosoniveum, and Torrubiella homopterorum with LT 50 between 120 and 150 min irradiation. The four species in cluster 1 had the lowest UV tolerance: Lecanicillium aphanocladii, Beauveria bassiana, Tolypocladium cylindrosporum, and Tolypocladium inflatum with LT 50  < 120 min irradiation. The QSUN Xenon Test Chamber XE3 is often used by the pharmaceutical and automotive industry to test light stability and weathering, respectively, but it was never used to evaluate fungal tolerance to full-spectrum solar radiation before. We conclude that the equipment provided an excellent tool for testing realistic tolerances of fungi to full-spectrum solar radiation of microbial agents for insect biological control in agriculture. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Utility of antenatal clinical factors for prediction of postpartum outcomes in women with gestational diabetes mellitus (GDM).

PubMed

Ingram, Emily R; Robertson, Iain K; Ogden, Kathryn J; Dennis, Amanda E; Campbell, Joanne E; Corbould, Anne M

2017-06-01

Gestational diabetes mellitus (GDM) is associated with life-long increased risk of type 2 diabetes: affected women are advised to undergo oral glucose tolerance testing (OGTT) at 6-12 weeks postpartum, then glucose screening every 1-3 years. We investigated whether in women with GDM, antenatal clinical factors predicted postpartum abnormal glucose tolerance and compliance with screening. In women with GDM delivering 2007 to mid-2009 in a single hospital, antenatal/obstetric data and glucose tests at 6-12 weeks postpartum and during 5.5 years post-pregnancy were retrospectively collected. Predictors of return for testing and abnormal glucose tolerance were identified using multivariate analysis. Of 165 women, 117 (70.9%) returned for 6-12 week postpartum OGTT: 23 (19.6%) were abnormal. Smoking and parity, independent of socioeconomic status, were associated with non-return for testing. Fasting glucose ≥5.4 mmol/L on pregnancy OGTT predicted both non-return for testing and abnormal OGTT. During 5.5 years post-pregnancy, 148 (89.7%) women accessed glucose screening: nine (6.1%) developed diabetes, 33 (22.3%) had impaired fasting glucose / impaired glucose tolerance. Predictors of abnormal glucose tolerance were fasting glucose ≥5.4 mmol/L and 2-h glucose ≥9.3 mmol/L on pregnancy OGTT (~2.5-fold increased risk), and polycystic ovary syndrome (~3.4 fold increased risk). Risk score calculation, based on combined antenatal factors, did not improve predictions. Antenatal clinical factors were modestly predictive of return for testing and abnormal glucose tolerance post-pregnancy in women with GDM. Risk score calculations were ineffective in predicting outcomes: risk scores developed in other populations require validation. Ongoing glucose screening is indicated for all women with GDM. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Multiple cold resistance loci confer the high cold tolerance adaptation of Dongxiang wild rice (Oryza rufipogon) to its high-latitude habitat.

PubMed

Mao, Donghai; Yu, Li; Chen, Dazhou; Li, Lanying; Zhu, Yuxing; Xiao, Yeqing; Zhang, Dechun; Chen, Caiyan

2015-07-01

Dongxiang wild rice is phylogenetically close to temperate japonica and contains multiple cold resistance loci conferring its adaptation to high-latitude habitat. Understanding the nature of adaptation in wild populations will benefit crop breeding in the development of climate-resilient crop varieties. Dongxiang wild rice (DXWR), the northernmost common wild rice known, possesses a high degree of cold tolerance and can survive overwintering in its native habitat. However, to date, it is still unclear how DXWR evolved to cope with low-temperature environment, resulting in limited application of DXWR in rice breeding programs. In this study, we carried out both QTL mapping and phylogenetic analysis to discern the genetic mechanism underlying the strong cold resistance. Through a combination of interval mapping and single locus analysis in two genetic populations, at least 13 QTLs for seedling cold tolerance were identified in DXWR. A phylogenetic study using both genome-wide InDel markers and markers associated with cold tolerance loci reveals that DXWR belongs to the Or-III group, which is most closely related to cold-tolerant Japonica rice rather than to the Indica cultivars that are predominant in the habitat where DXWR grows. Our study paves the way toward an understanding of the nature of adaptation to a northern habitat in O. rufipogon. The QTLs identified in DXWR in this study will be useful for molecular breeding of cold-tolerant rice.

Materials and processes laboratory composite materials characterization task, part 1. Damage tolerance

NASA Technical Reports Server (NTRS)

Nettles, A. T.; Tucker, D. S.; Patterson, W. J.; Franklin, S. W.; Gordon, G. H.; Hart, L.; Hodge, A. J.; Lance, D. G.; Russel, S. S.

1991-01-01

A test run was performed on IM6/3501-6 carbon-epoxy in which the material was processed, machined into specimens, and tested for damage tolerance capabilities. Nondestructive test data played a major role in this element of composite characterization. A time chart was produced showing the time the composite material spent within each Branch or Division in order to identify those areas which produce a long turnaround time. Instrumented drop weight testing was performed on the specimens with nondestructive evaluation being performed before and after the impacts. Destructive testing in the form of cross-sectional photomicrography and compression-after-impact testing were used. Results show that the processing and machining steps needed to be performed more rapidly if data on composite material is to be collected within a reasonable timeframe. The results of the damage tolerance testing showed that IM6/3501-6 is a brittle material that is very susceptible to impact damage.

Regulatory Focus Affects Physician Risk Tolerance

PubMed Central

Veazie, Peter J.; McIntosh, Scott; Chapman, Benjamin P.; Dolan, James G.

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention – regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (P=0.01). The Cohen’s d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (P=0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor. PMID:25431799

Flight test results of the Strapdown hexad Inertial Reference Unit (SIRU). Volume 1: Flight test summary

NASA Technical Reports Server (NTRS)

Hruby, R. J.; Bjorkman, W. S.

1977-01-01

Flight test results of the strapdown inertial reference unit (SIRU) navigation system are presented. The fault-tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance.

Does patent ductus arteriosus affect feed tolerance in preterm neonates?

PubMed

Patole, S K; Kumaran, V; Travadi, J N; Brooks, J M; Doherty, D A

2007-01-01

Patent ductus arteriosus (PDA), especially PDA with sepsis, has been reported as a risk factor for feed intolerance in preterm neonates. In this study, the start to full feeds interval was found to be longest in preterm neonates (

VKOR variant and sex are the main influencing factors on bromadiolone tolerance of the house mouse (Mus musculus L.).

PubMed

Šćepović, Tanja; Jokić, Goran; Esther, Alexandra; Kataranovski, Dragan; Vukša, Petar; Đedović, Suzana; Vukša, Marina

2016-03-01

After reports of management problems in practice, a survey was conducted to determine the presence of bromadiolone-resistant animals in different house mouse (Mus musculus L.) populations in Serbia. A 21 day no-choice feeding test was carried out to examine the resistance of house mice to bromadiolone. Eighty house mice collected from four locations (ten males and ten females per location) were tested for bromadiolone tolerance. Surviving animals and their F1 offspring were screened for mutations. The influence of VKOR variant, zygosity and sex on bromadiolone tolerance was analysed. Bait intake and changes in body weight revealed different animal responses regarding susceptibility or resistance. Leu128Ser, Tyr139Cys and a new Ala21Thr polymorphism were detected in wild-born survivors and their F1 generation. However, not every individual with the polymorphisms Leu128Ser and Tyr139Cys survived the feeding test. VKOR variants and sex caused variations in bromadiolone tolerance. For the first time it was shown that the VKOR variant, along with sex, is responsible for bromadiolone tolerance in house mice. Other factors influencing bromadiolone tolerance, including sex-specific factors, cannot be excluded. The tolerance levels of VKOR variants should be determined in further studies in order to evaluate the effectiveness of bromadiolone in sustainable management. © 2015 Society of Chemical Industry.

Multi-version software reliability through fault-avoidance and fault-tolerance

NASA Technical Reports Server (NTRS)

Vouk, Mladen A.; Mcallister, David F.

1989-01-01

A number of experimental and theoretical issues associated with the practical use of multi-version software to provide run-time tolerance to software faults were investigated. A specialized tool was developed and evaluated for measuring testing coverage for a variety of metrics. The tool was used to collect information on the relationships between software faults and coverage provided by the testing process as measured by different metrics (including data flow metrics). Considerable correlation was found between coverage provided by some higher metrics and the elimination of faults in the code. Back-to-back testing was continued as an efficient mechanism for removal of un-correlated faults, and common-cause faults of variable span. Software reliability estimation methods was also continued based on non-random sampling, and the relationship between software reliability and code coverage provided through testing. New fault tolerance models were formulated. Simulation studies of the Acceptance Voting and Multi-stage Voting algorithms were finished and it was found that these two schemes for software fault tolerance are superior in many respects to some commonly used schemes. Particularly encouraging are the safety properties of the Acceptance testing scheme.

Early genetic testing of coastal Douglas-fir for Swiss needle cast tolerance.

Treesearch

Fatih Temel; G.R. Johnson; W.T. Adams

2005-01-01

The possibility of early testing coastal Douglas-fir (Pseudotsuga menziesii var. menziesii (Mirb.) Franco) for Swiss needle cast (SNC; caused by Phaeocryptopus gaeumannii (Rohde) Petrak) tolerance was investigated using 55 Douglas-fir families from western Oregon. Seedlings were inoculated with P...

Factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus: decision-curve analysis.

PubMed

Kondo, M; Nagao, Y; Mahbub, M H; Tanabe, T; Tanizawa, Y

2018-04-29

To identify factors predicting early postpartum glucose intolerance in Japanese women with gestational diabetes mellitus, using decision-curve analysis. A retrospective cohort study was performed. The participants were 123 Japanese women with gestational diabetes who underwent 75-g oral glucose tolerance tests at 8-12 weeks after delivery. They were divided into a glucose intolerance and a normal glucose tolerance group based on postpartum oral glucose tolerance test results. Analysis of the pregnancy oral glucose tolerance test results showed predictive factors for postpartum glucose intolerance. We also evaluated the clinical usefulness of the prediction model based on decision-curve analysis. Of 123 women, 78 (63.4%) had normoglycaemia and 45 (36.6%) had glucose intolerance. Multivariable logistic regression analysis showed insulinogenic index/fasting immunoreactive insulin and summation of glucose levels, assessed during pregnancy oral glucose tolerance tests (total glucose), to be independent risk factors for postpartum glucose intolerance. Evaluating the regression models, the best discrimination (area under the curve 0.725) was obtained using the basic model (i.e. age, family history of diabetes, BMI ≥25 kg/m 2 and use of insulin during pregnancy) plus insulinogenic index/fasting immunoreactive insulin <1.1. Decision-curve analysis showed that combining insulinogenic index/fasting immunoreactive insulin <1.1 with basic clinical information resulted in superior net benefits for prediction of postpartum glucose intolerance. Insulinogenic index/fasting immunoreactive insulin calculated using oral glucose tolerance test results during pregnancy is potentially useful for predicting early postpartum glucose intolerance in Japanese women with gestational diabetes. © 2018 Diabetes UK.

Feeding Intervals in Premature Infants ≤1750 g: An Integrative Review.

PubMed

Binchy, Áine; Moore, Zena; Patton, Declan

2018-06-01

The timely establishment of enteral feeds and a reduction in the number of feeding interruptions are key to achieving optimal nutrition in premature infants. Nutritional guidelines vary widely regarding feeding regimens and there is not a widely accepted consensus on the optimal feeding interval. To critically examine the evidence to determine whether there is a relationship to feeding intervals and feeding outcomes in premature infants. A systematic review of the literature in the following databases: PubMed, CINAHL, Embase and the Cochrane Library. The search strategy used the terms infant premature, low birth weight, enteral feeding, feed tolerance and feed intervals. Search results yielded 10 studies involving 1269 infants (birth weight ≤1750 g). No significant differences in feed intolerance, growth, or incidence of necrotizing enterocolitis were observed. Evidence suggests that infants fed at 2 hourly intervals reached full feeds faster than at 3 hourly intervals, had fewer days on parenteral nutrition, and fewer days in which feedings were withheld. Decrease in the volume of gastric residuals and feeding interruptions were observed in the infants fed at 3 hourly intervals than those who were continuously fed. Reducing the feed interval from 3 to 2 hourly increases nurse workload, yet may improve feeding outcomes by reducing the time to achieve full enteral feeding. Studies varied greatly in the definition and management of feeding intolerance and in how outcomes were measured, analyzed, and reported. The term "intermittent" is used widely but can refer to a 2 or 3 hourly interval.

Using Ice Cream for Diagnosis of Diabetes Mellitus and Impaired Glucose Tolerance: An Alternative to the Oral Glucose Tolerance Test.

PubMed

Chanprasertpinyo, Wandee; Bhirommuang, Nattapimon; Surawattanawiset, Titiporn; Tangsermwong, Thanwarin; Phanachet, Pariya; Sriphrapradang, Chutintorn

2017-12-01

Oral glucose tolerance test (OGTT) is a sensitive and reliable test for diabetes mellitus and impaired glucose tolerance (IGT). However, poor patient tolerance of glucose solutions is common. We aim to compare the diagnostic value of an ice cream test with a standard OGTT. A total of 104 healthy adults were randomly assigned to either 75-g OGTT or ice cream, followed by a crossover to the other test. Most patients were females (71%). Mean age was 37 ± 12 years, and body mass index was 24.2 ± 3.9kg/m 2 . Diabetes mellitus and IGT, as diagnosed by 75-g OGTT, were 4.8% and 6.7%, respectively. The 2-hour plasma glucose levels were 110 ± 55.5mg/dL with 75-g glucose and 97.52 ± 40.7mg/dL with ice cream. The correlation coefficient of 2-hour plasma glucose for the 2 tests was 0.82 (95% CI: 0.75-0.87; P < 0.001). Discordant diagnostic results, based on 2-hour plasma glucose levels, were 9.61%. By using a combination of fasting plasma glucose and 2-hour plasma glucose values, the ice cream test would have missed 5.76% of those at high risk for diabetes mellitus (impaired fasting glucose and IGT) or diabetes. An ice cream test may serve as an alternative to a 75-g OGTT. Before applying this test in clinical practice, it needs to be validated in a larger population. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Timing and Frequency of Sublethal Exposure Modifies the Induction and Retention of Increased Insecticide Tolerance in Wood Frogs (Lithobates sylvaticus).

PubMed

Jones, Devin K; Yates, Erika K; Mattes, Brian M; Hintz, William D; Schuler, Matthew S; Relyea, Rick A

2018-05-22

While the paradigm for increased tolerance to pesticides has been by selection on constitutive (naïve) traits, recent research has shown it can also occur through phenotypic plasticity. However, the time period in which induction can occur, the duration of induced tolerance, and the influence of multiple induction events remain unknown. We hypothesized that the induction of increased pesticide tolerance is limited to early sensitive periods, the magnitude of induced tolerance depends on the number of exposures, and the retention of induced tolerance depends on the time elapsed after an exposure and the number of exposures. To test these hypotheses, we exposed wood frog tadpoles to either a no-carbaryl control (water) or 0.5 mg/L carbaryl at four time periods, and later tested their tolerance to carbaryl using time-to-death assays. We discovered that tadpoles induced increased tolerance early and midway, but not late, in our experiment and their constitutive tolerance increased with age. We found no difference in the magnitude of induced tolerance following one or two exposures. Lastly, induced pesticide tolerance was reversed within 6 d, but was retained only when tadpoles experienced all four consecutive exposures. Phenotypic plasticity provides an immediate response for sensitive amphibian larvae to early pesticide exposures and reduces phenotypic mismatches in aquatic environments contaminated by agrochemicals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Expressing analytical performance from multi-sample evaluation in laboratory EQA.

PubMed

Thelen, Marc H M; Jansen, Rob T P; Weykamp, Cas W; Steigstra, Herman; Meijer, Ron; Cobbaert, Christa M

2017-08-28

To provide its participants with an external quality assessment system (EQAS) that can be used to check trueness, the Dutch EQAS organizer, Organization for Quality Assessment of Laboratory Diagnostics (SKML), has innovated its general chemistry scheme over the last decade by introducing fresh frozen commutable samples whose values were assigned by Joint Committee for Traceability in Laboratory Medicine (JCTLM)-listed reference laboratories using reference methods where possible. Here we present some important innovations in our feedback reports that allow participants to judge whether their trueness and imprecision meet predefined analytical performance specifications. Sigma metrics are used to calculate performance indicators named 'sigma values'. Tolerance intervals are based on both Total Error allowable (TEa) according to biological variation data and state of the art (SA) in line with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Milan consensus. The existing SKML feedback reports that express trueness as the agreement between the regression line through the results of the last 12 months and the values obtained from reference laboratories and calculate imprecision from the residuals of the regression line are now enriched with sigma values calculated from the degree to which the combination of trueness and imprecision are within tolerance limits. The information and its conclusion to a simple two-point scoring system are also graphically represented in addition to the existing difference plot. By adding sigma metrics-based performance evaluation in relation to both TEa and SA tolerance intervals to its EQAS schemes, SKML provides its participants with a powerful and actionable check on accuracy.

Efficacy, acceptability and tolerability of the combined contraceptive ring, NuvaRing, compared with an oral contraceptive containing 30 microg of ethinyl estradiol and 3 mg of drospirenone.

PubMed

Ahrendt, Hans-Joachim; Nisand, Israel; Bastianelli, Carlo; Gómez, Maria Angeles; Gemzell-Danielsson, Kristina; Urdl, Wolfgang; Karskov, Birgit; Oeyen, Luc; Bitzer, Johannes; Page, Geert; Milsom, Ian

2006-12-01

This randomized multicenter, open-label, trial compared efficacy, acceptability, tolerability and compliance of NuvaRing with a combined oral contraceptive (COC), containing 30 microg of ethinyl estradiol (EE) and 3 mg of drospirenone. In this 13-cycle study, 983 women were randomized and treated (intent-to-treat population) with NuvaRing or COC. One in-treatment pregnancy occurred with NuvaRing (Pearl Index=0.25) (95% confidence interval [CI]: 0.006, 1.363) and four with the COC (Pearl Index=0.99) (95% CI: 0.269, 2.530). For both groups, compliance (89.2% NuvaRing, 85.5% COC) and satisfaction (84% NuvaRing; 87% COC) were high; the vast majority of women found NuvaRing easy to insert (96%) and remove (97%). Tolerability was similar; the most frequent adverse events with NuvaRing were related to ring use, whereas estrogen-related events were more common with the COC. NuvaRing has comparable efficacy and tolerability to a COC containing 30 microg of EE and 3 mg drospirenone. User acceptability of both methods was high.

Comparison of 70 deg tilt, LBNP, and passive standing as measures of orthostatic tolerance

NASA Technical Reports Server (NTRS)

Hyatt, K. H.; Jacobson, L. B.; Schneider, V. S.

1975-01-01

The present study was performed to assess the reliability of lower body negative pressure (LBNP) as a test of orthostatic tolerance. The need for this assessment arose from the prior observation in this laboratory that some subjects show wide day-to-day variation in heart rate responses to LBNP. The extent of these variations was so great as to raise a serious question as to the value of LBNP as a measure of study-induced alterations (e.g., those produced by bedrest or weightlessness) in orthostatic tolerance. Five healthy volunteers were subjected to a series of tests, consisting of 70 deg tilt, LBNP, and passive standing, on three occasions preceding and three occasions following a 2-week period of bedrest. Study results show that it is possible to subdivide the volunteers into subgroups which show either great or little day-to-day variability in any of the three tests. All three tests revealed bedrest-induced alterations in orthostatic tolerance quite adequately. Of the three tests studied, LBNP most frequently resulted in the largest test-induced heart rate alterations, followed by quiet standing and, finally 70 deg tilt.

Tolerance limit value of brightness and contrast adjustment on digitized radiographs

NASA Astrophysics Data System (ADS)

Utami, S. N.; Kiswanjaya, B.; Syahraini, S. I.; Ustriyana, P.

2017-08-01

The aim of this study was to measure the tolerance limit value of brightness and contrast adjustment on digitized radiograph with apical periodontitis and early apical abscess. Brightness and contrast adjustment on 60 periapical radiograph with apical periodontitis and early apical abscess made by 2 observers. Reliabilities tested by Cohen’s Kappa Coefficient and significance tested by wilcoxon test. Tolerance limit value of brightness and contrast adjustment for apical periodontitis is -5 and +5, early apical abscess is -10 and +10, and both is -5 and +5. Brightness and contrast adjustment which not appropriate can alter the evaluation and differential diagnosis of periapical lesion.

Four applications of permutation methods to testing a single-mediator model.

PubMed

Taylor, Aaron B; MacKinnon, David P

2012-09-01

Four applications of permutation tests to the single-mediator model are described and evaluated in this study. Permutation tests work by rearranging data in many possible ways in order to estimate the sampling distribution for the test statistic. The four applications to mediation evaluated here are the permutation test of ab, the permutation joint significance test, and the noniterative and iterative permutation confidence intervals for ab. A Monte Carlo simulation study was used to compare these four tests with the four best available tests for mediation found in previous research: the joint significance test, the distribution of the product test, and the percentile and bias-corrected bootstrap tests. We compared the different methods on Type I error, power, and confidence interval coverage. The noniterative permutation confidence interval for ab was the best performer among the new methods. It successfully controlled Type I error, had power nearly as good as the most powerful existing methods, and had better coverage than any existing method. The iterative permutation confidence interval for ab had lower power than do some existing methods, but it performed better than any other method in terms of coverage. The permutation confidence interval methods are recommended when estimating a confidence interval is a primary concern. SPSS and SAS macros that estimate these confidence intervals are provided.

Application of the Speed-Duration Relationship to Normalize the Intensity of High-Intensity Interval Training

PubMed Central

Ferguson, Carrie; Wilson, John; Birch, Karen M.; Kemi, Ole J.

2013-01-01

The tolerable duration of continuous high-intensity exercise is determined by the hyperbolic Speed-tolerable duration (S-tLIM) relationship. However, application of the S-tLIM relationship to normalize the intensity of High-Intensity Interval Training (HIIT) has yet to be considered, with this the aim of present study. Subjects completed a ramp-incremental test, and series of 4 constant-speed tests to determine the S-tLIM relationship. A sub-group of subjects (n = 8) then repeated 4 min bouts of exercise at the speeds predicted to induce intolerance at 4 min (WR4), 6 min (WR6) and 8 min (WR8), interspersed with bouts of 4 min recovery, to the point of exercise intolerance (fixed WR HIIT) on different days, with the aim of establishing the work rate that could be sustained for 960 s (i.e. 4×4 min). A sub-group of subjects (n = 6) also completed 4 bouts of exercise interspersed with 4 min recovery, with each bout continued to the point of exercise intolerance (maximal HIIT) to determine the appropriate protocol for maximizing the amount of high-intensity work that can be completed during 4×4 min HIIT. For fixed WR HIIT tLIM of HIIT sessions was 399±81 s for WR4, 892±181 s for WR6 and 1517±346 s for WR8, with total exercise durations all significantly different from each other (P<0.050). For maximal HIIT, there was no difference in tLIM of each of the 4 bouts (Bout 1: 229±27 s; Bout 2: 262±37 s; Bout 3: 235±49 s; Bout 4: 235±53 s; P>0.050). However, there was significantly less high-intensity work completed during bouts 2 (153.5±40. 9 m), 3 (136.9±38.9 m), and 4 (136.7±39.3 m), compared with bout 1 (264.9±58.7 m; P>0.050). These data establish that WR6 provides the appropriate work rate to normalize the intensity of HIIT between subjects. Maximal HIIT provides a protocol which allows the relative contribution of the work rate profile to physiological adaptations to be considered during alternative intensity-matched HIIT protocols. PMID:24244266

Efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia.

PubMed

Shenoy, K T; Veenasree; Leena, K B

2003-06-01

To document the clinical efficacy and tolerability of itopride hydrochloride in patients with non-ulcer dyspepsia an open-label, non-comparative study, was undertaken at the Medical College, Thiruvananthapuram, among patients with endoscopically confirmed diagnosis of non-ulcer dyspepsia or chronic gastritis. Itopride hydrochloride 50 mg (1 tablet) thrice a day for 2 weeks was administered among them. Relief of symptoms at the end of two weeks treatment, assessed as marked/complete, moderate, slight, none or worse; QT interval on ECG; adverse events; haemogram; serum chemistry for hepatic and renal functions. None had QT prolongation on ECG. At the end of 2 weeks' treatment, moderate to complete relief of symptoms was reported by 22 patients (73%), whereas 5 (17%) reproted slight improvement, and 3 (10%) reported no improvement. Clinical tolerability was excellent in 28 patients (93%) and good in 2 (7%). None of the patients had any prolongation of QT on ECG, nor did any patient show any abnormality in haemogram or serum chemistry during the treatment.

High Resolution Mapping of QTLs for Heat Tolerance in Rice Using a 5K SNP Array.

PubMed

Ps, Shanmugavadivel; Sv, Amitha Mithra; Prakash, Chandra; Mk, Ramkumar; Tiwari, Ratan; Mohapatra, Trilochan; Singh, Nagendra Kumar

2017-12-01

Heat stress is one of the major abiotic threats to rice production, next to drought and salinity stress. Incidence of heat stress at reproductive phase of the crop results in abnormal pollination leading to floret sterility, low seed set and poor grain quality. Identification of QTLs and causal genes for heat stress tolerance at flowering will facilitate breeding for improved heat tolerance in rice. In the present study, we used 272 F 8 recombinant inbred lines derived from a cross between Nagina22, a well-known heat tolerant Aus cultivar and IR64, a heat sensitive popular Indica rice variety to map the QTLs for heat tolerance. To enable precise phenotyping for heat stress tolerance, we used a controlled phenotyping facility available at ICAR-Indian Institute of Wheat and Barley Research, Karnal, India. Based on 'days to 50% flowering' data of the RILs, we followed staggered sowing to synchronize flowering to impose heat stress at uniform stage. Using the Illumina infinium 5K SNP array for genotyping the parents and the RILs, and stress susceptibility and stress tolerance indices (SSI and STI) of percent spikelet sterility and yield per plant (g), we identified five QTLs on chromosomes 3, 5, 9 and 12. The identified QTLs explained phenotypic variation in the range of 6.27 to 21. 29%. Of these five QTLs, two high effect QTLs, one novel (qSTIPSS9.1) and one known (qSTIY5.1/qSSIY5.2), were mapped in less than 400 Kbp genomic regions, comprising of 65 and 54 genes, respectively. The present study identified two major QTLs for heat tolerance in rice in narrow physical intervals, which can be employed for crop improvement by marker assisted selection (MAS) after development of suitable scorable markers for breeding of high yielding heat tolerant rice varieties. This is the first report of a major QTL for heat tolerance on chromosome 9 of rice. Further, a known QTL for heat tolerance on chromosome 5 was narrowed down from 23 Mb to 331 Kbp in this study.

Resistance of a northwestern crayfish, Pacifastacus leniusculus (Dana), to elevated temperatures

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

Becker, C.D.; Genoway, R.G.; Merrill, J.A.

1975-04-01

Pacifastacus leniusculus from two populations in Washington State, the central Columbia River and a small tributary, were acclimated at 5/sup 0/C intervals and exposed to elevated temperatures in 48 hour thermal bioassays. The upper lethal temperature for both crayfish populations increased relatively slightly, from about 28.5 to 31.5/sup 0/C, over the entire acclimation range. A rise of 1/sup 0/C in test temperature often represented the difference between zero and total mortality when lethal limits were approached. The ultimate upper lethal temperature was near 32 to 33/sup 0/C. Statistically significant differences in thermal resistance patterns (slope and spacing of regression lines)more » occurred between the two crayfish populations at all acclimation levels, but resistance in terms of eventual mortality was similar for practical purposes. Moulting individuals were particularly susceptible to high temperature stress. Mature, pre-breeding female crayfish from the Columbia River during fall appeared less resistant, and egg-bearing females during winter more resistant, than other individuals. Larger crayfish from the Columbia River were slightly less resistant to elevated temperatures than smaller ones, and females were more resistant than males. The upper temperature triangle for P. leniusculus encompasses an area of 424/sup 0/C/sup 2/. This freshwater decapod is more tolerant of elevated temperatures than native salmonids, but less tolerant than some introduced ''warmwater'' fish.« less

The influence of urea and nitrate nutrients on the bioavailability and toxicity of nickel to Prorocentrum donghaiense (Dinophyta) and Skeletonema costatum (Bacillariophyta).

PubMed

Huang, Xu-Guang; Lin, Xie-Chang; Li, Shun-Xing; Xu, Song-Li; Liu, Feng-Jiao

2016-12-01

Nitrogen nutrients and nickel(Ni) are ubiquitous in aquatic environments, and they are important for primary production of ocean ecosystem. This study examined the interaction of nitrogen nutrients (specifically urea and nitrate) and Ni on chlorophyll (Chl a) concentration and photosynthesis parameters values of Prorocentrum donghaiense and Skeletonema costatum. The data presented here indicate that low concentration of Ni for P. donghaiense and S. costatum can enhance both Chl a concentration and photosynthesis parameters values when grown in urea containing environment. Despite this increase there was also an observed depression in both species tested when incubated in high concentration of Ni for P. donghaiense and S. costatum regardless of incubating in urea or nitrate. Additionally, EC 50 values of Chl a and Fv/Fm for Ni at different time intervals were calculated in this study. These observations indicated that the Ni tolerance was higher in P. donghaiense as compared to S. costatum. The Ni tolerance of P. donghaiense incubated in urea was higher than that incubating in nitrate. The same phenomenon was not observed in S. costatum, which indicated that the influence of urea was dependent on the species investigated. Thus, urea input could impact Ni bioavailability and toxicity, and then affect the biodynamics thereafter. Copyright © 2016. Published by Elsevier B.V.

Personality traits and abnormal glucose regulation in middle-aged Swedish men and women.

PubMed

Eriksson, Anna-Karin; Gustavsson, J Petter; Hilding, Agneta; Granath, Fredrik; Ekbom, Anders; Ostenson, Claes-Göran

2012-01-01

To examine associations between personality and abnormal glucose regulation. This cross-sectional study comprised 2152 men and 3143 women (43-66 years). Oral glucose tolerance test identified 316 men and 213 women with previously unknown impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT, or type 2 diabetes. Personality traits antagonism (low agreeableness), impulsivity (low conscientiousness), hedonic capacity (high extraversion), negative affectivity (high neuroticism) and alexithymia (low openness) were measured by a self-report inventory. Based on distribution of scores, responses were divided into "low" (<1 SD), "middle" (±1 SD) and "high" (>1 SD). Middle groups were considered reference groups. Prevalence odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. In men, OR for low antagonism was 0.3 (CI 0.2-0.6) (age- and multi-adjusted models) while in women, neither high nor low antagonism was associated to abnormal glucose regulation. Men and women with high hedonic capacity had ORs 0.5 (0.3-0.9) and 0.6 (0.4-1.0), respectively (age- and multi-adjusted models). The other scales illustrated no significant associations. No elevated risk of abnormal glucose regulation was observed for deviating scores on personality scales. Instead, reduced risks were indicated in men with low antagonism, and in men and women with high hedonic capacity. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cardiorespiratory assessment of 24-hour crash-diet effects on altitude, +Gz, and fatigue tolerances.

DOT National Transportation Integrated Search

1981-02-01

Eleven male surrogates of general aviation pilots, 25-40 years old, were tested for altitude, +Gz, and fatigue tolerances with and without previous fasting for 24 h. Testing included 2 min of lower body negative pressure (LBNP) at -40 torr (equivalen...

77 FR 56782 - Bifenthrin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-14

..., hay. Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food... OCSPP test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp and select ``Test Methods and Guidelines.'' C. How can I file an objection or hearing request? Under...

78 FR 55635 - Prometryn; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-11

.... Interregional Research Project Number 4 (IR-4) requested these tolerances under the Federal Food, Drug, and... test guidelines referenced in this document electronically, please go to http://www.epa.gov/ocspp and select ``Test Methods and Guidelines. C. How can I file an objection or hearing request? Under FFDCA...

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Effect of work and recovery durations on W' reconstitution during intermittent exercise.

PubMed

Skiba, Philip F; Jackman, Sarah; Clarke, David; Vanhatalo, Anni; Jones, Andrew M

2014-07-01

We recently presented an integrating model of the curvature constant of the hyperbolic power-time relationship (W') that permits the calculation of the W' balance (W'BAL) remaining at any time during intermittent exercise. Although a relationship between recovery power and the rate of W' recovery was demonstrated, the effect of the length of work or recovery intervals remains unclear. After determining VO2max, critical power, and W', 11 subjects completed six separate exercise tests on a cycle ergometer on different days, and in random order. Tests consisted of a period of intermittent severe-intensity exercise until the subject depleted approximately 50% of their predicted W'BAL, followed by a constant work rate (CWR) exercise bout until exhaustion. Work rates were kept constant between trials; however, either work or recovery durations during intermittent exercise were varied. The actual W' measured during the CWR (W'ACT) was compared with the amount of W' predicted to be available by the W'BAL model. Although some differences between W'BAL and W'ACT were noted, these amounted to only -1.6 ± 1.1 kJ when averaged across all conditions. The W'ACT was linearly correlated with the difference between VO2 at the start of CWR and VO2max (r = 0.79, P < 0.01). The W'BAL model provided a generally robust prediction of CWR W'. There may exist a physiological optimum formulation of work and recovery intervals such that baseline VO2 can be minimized, leading to an enhancement of subsequent exercise tolerance. These results may have important implications for athletic training and racing.

[Interval hypoxic-hyperoxic training in the treatment of the metabolic syndrome].

PubMed

Glazachev, O S; Zvenigorodskaia, L A; Dudnik, E N; Iartseva, L A; Mishchenkova, T V; Platonenko, A V; Spirina, G K

2010-01-01

to investigate the possibility of a new method--interval hypo-hyperoxic training (IHHT)--in the correction of the individual components of metabolic syndrome. The study included 35 patients with metabolic syndrome (alimentary obesity 1-3rd stage [BMI over 30 kg/m2], violation of carbohydrate tolerance or diabetes mellitus type II, hypertension and dyslipidemia). All patients were random separated into three groups: control (11 pers., basic therapy), trial 1 (13 pers. who have undergone 12 procedures of the IHHT) and trial 2 (11 pers. who have undergone IHHT in parallel with systemic hyperthermia and vibrating massage hardware). Course duration was 21 days average. Prior to the course procedures IHHT and the 3-day 4 upon completion all patients were fully examined. This examination included history taking, assessment of diet, psychometric testing, counseling psychologist to determine the type of feeding behavior, anthropometric measurements; body impendansemetria, biochemical study of blood determining the level of total cholesterol, HDL, LDL, TG, fasting plasma glucose (GP), 6-minute walk test to assess physical performance. Was established that the use of hypo-hyperoxic exercise (alone or in combination with systemic hyperthermia and hardware vibratory) leads to a significant reduction in body weight. It mainly arise by reducing fat mass accompanied by a reduction of total cholesterol, LDL, GPN, optimization of blood pressure, increased hypoxic stability, physical endurance, improved mental status. At individual selection of the course structure, dosing of hypoxic effects, combined with other physiotherapy method has some promise in treatment and rehabilitation of patients with metabolic syndrome.

Effect of resin on impact damage tolerance of graphite/epoxy laminates

NASA Technical Reports Server (NTRS)

Williams, J. G.; Rhodes, M. D.

1982-01-01

Twenty-four different epoxy resin systems were evaluated by a variety of test techniques to identify materials that exhibited improved impact damage tolerance in graphite/epoxy composite laminates. Forty-eight-ply composite panels of five of the material systems were able to sustain 100 m/s impact by a 1.27-cm-diameter aluminum projectile while statically loaded to strains of 0.005. Of the five materials with the highest tolerance to impact, two had elastomeric additives, two had thermoplastic additives, and one had a vinyl modifier; all the five systems used bisphenol A as the base resin. An evaluation of test results shows that the laminate damage tolerance is largely determined by the resin tensile properties, and that improvements in laminate damage tolerance are not necessarily made at the expense of room-temperature mechanical properties. The results also suggest that a resin volume fraction of 40 percent or greater may be required to permit the plastic flow between fibers necessary for improved damage tolerance.

Tolerability of 2.5% Lidocaine/Prilocaine Hydrogel in Children Undergoing Cryotherapy for Molluscum Contagiosum.

PubMed

Gobbato, André A M; Babadópulos, Tainah; Gobbato, Cintia A R S; Moreno, Ronilson A; Gagliano-Jucá, Thiago; De Nucci, Gilberto

2016-05-01

The tolerability of a 2.5% lidocaine/prilocaine hydrogel (Nanorap, Biolab Indústria Farmacêutica Ltd., Sao Paulo, Brazil) was evaluated in 20 children ages 2 to 11 years undergoing cryotherapy for molluscum contagiosum (MC). The product was well tolerated, with only two children presenting with eczema at the application site. These adverse reactions were considered unlikely to be related to the test product, because a patch test was negative in one of the individuals and the other event occurred in only one of the two treated areas. Nanorap is an efficacious and well-tolerated option for topical anesthesia in children undergoing cryotherapy for MC. © 2016 Wiley Periodicals, Inc.

Is the OJIP Test a Reliable Indicator of Winter Hardiness and Freezing Tolerance of Common Wheat and Triticale under Variable Winter Environments?

PubMed Central

Rapacz, Marcin; Sasal, Monika; Kalaji, Hazem M.; Kościelniak, Janusz

2015-01-01

OJIP analysis, which explores changes in photosystem II (PSII) photochemical performance, has been used as a measure of plant susceptibility to stress. However, in the case of freezing tolerance and winter hardiness, which are highly environmentally variable, the use of this method can give ambiguous results depending on the species as well as the sampling year and time. To clarify this issue, we performed chlorophyll fluorescence measurements over three subsequent winters (2010/11, 2011/12 and 2012/13) on 220 accessions of common winter wheat and 139 accessions of winter triticale. After freezing, leaves were collected from cold-acclimated plants in the laboratory and field-grown plants. Observations of field survival in seven locations across Poland and measurements of freezing tolerance of the studied plants were also recorded. Our results confirm that the OJIP test is a reliable indicator of winter hardiness and freezing tolerance of common wheat and triticale under unstable winter environments. Regardless of species, the testing conditions giving the most reliable results were identical, and the reliability of the test could be easily checked by analysis of some relationships between OJIP-test parameters. We also found that triticale is more winter hardy and freezing tolerant than wheat. In addition, the two species were characterized by different patterns of photosynthetic apparatus acclimation to cold. PMID:26230839

Is the OJIP Test a Reliable Indicator of Winter Hardiness and Freezing Tolerance of Common Wheat and Triticale under Variable Winter Environments?

PubMed

Rapacz, Marcin; Sasal, Monika; Kalaji, Hazem M; Kościelniak, Janusz

2015-01-01

OJIP analysis, which explores changes in photosystem II (PSII) photochemical performance, has been used as a measure of plant susceptibility to stress. However, in the case of freezing tolerance and winter hardiness, which are highly environmentally variable, the use of this method can give ambiguous results depending on the species as well as the sampling year and time. To clarify this issue, we performed chlorophyll fluorescence measurements over three subsequent winters (2010/11, 2011/12 and 2012/13) on 220 accessions of common winter wheat and 139 accessions of winter triticale. After freezing, leaves were collected from cold-acclimated plants in the laboratory and field-grown plants. Observations of field survival in seven locations across Poland and measurements of freezing tolerance of the studied plants were also recorded. Our results confirm that the OJIP test is a reliable indicator of winter hardiness and freezing tolerance of common wheat and triticale under unstable winter environments. Regardless of species, the testing conditions giving the most reliable results were identical, and the reliability of the test could be easily checked by analysis of some relationships between OJIP-test parameters. We also found that triticale is more winter hardy and freezing tolerant than wheat. In addition, the two species were characterized by different patterns of photosynthetic apparatus acclimation to cold.

Flight test results of the strapdown hexad inertial reference unit (SIRU). Volume 2: Test report

NASA Technical Reports Server (NTRS)

Hruby, R. J.; Bjorkman, W. S.

1977-01-01

Results of flight tests of the Strapdown Inertial Reference Unit (SIRU) navigation system are presented. The fault tolerant SIRU navigation system features a redundant inertial sensor unit and dual computers. System software provides for detection and isolation of inertial sensor failures and continued operation in the event of failures. Flight test results include assessments of the system's navigational performance and fault tolerance. Performance shortcomings are analyzed.

Assessment of biochemical mechanisms of tolerance to chlorpyrifos in ancient and contemporary Daphnia pulicaria genotypes.

PubMed

Simpson, Adam M; Jeyasingh, Punidan D; Belden, Jason B

2017-12-01

The evolution of tolerance to environmental contaminants in non-target taxa has been largely studied by comparing extant populations experiencing contrasting exposure. Previous research has demonstrated that "resurrected" genotypes from a population of Daphnia pulicaria express temporal variation in sensitivity to the insecticide chlorpyrifos. Ancient genotypes (1301-1646AD.) were on average more sensitive to this chemical compared to the contemporary genotypes (1967-1977AD.). To determine the physiological mechanisms of tolerance, a series of biochemical assays was performed on three ancient and three contemporary genotypes; these six genotypes exhibited the most sensitive and most tolerant phenotypes within the population, respectively. Metabolic tolerance mechanisms were evaluated using acute toxicity testing, while target-site tolerance was assessed via in vitro acetylcholinesterase (AChE) assays. Acute toxicity tests were conducted using i) the toxic metabolite chlorpyrifos-oxon (CPF-oxon) and ii) CPF-oxon co-applied with piperonyl butoxide (PBO), a known Phase-I metabolic inhibitor. Both series of toxicity tests reduced the mean variation in sensitivity between tolerant and sensitive genotypes. Exposure to CPF-O reduced the disparity from a 4.7-fold to 1.6-fold difference in sensitivity. The addition of PBO further reduced the variation to a 1.2-fold difference in sensitivity. In vitro acetylcholinesterase assays yielded no significant differences in constitutive activity or target-site sensitivity. These findings suggest that pathways involving Phase-I detoxification and/or bioactivation of chlorpyrifos play a significant role in dictating the microevolutionary trajectories of tolerance in this population. Copyright © 2017 Elsevier B.V. All rights reserved.

Does smoking abstinence influence distress tolerance? An experimental study comparing the response to a breath-holding test of smokers under tobacco withdrawal and under nicotine replacement therapy.

PubMed

Cosci, Fiammetta; Anna Aldi, Giulia; Nardi, Antonio Egidio

2015-09-30

Distress tolerance has been operationalized as task persistence in stressful behavioral laboratory tasks. According to the distress tolerance perspective, how an individual responds to discomfort/distress predicts early smoking lapses. This theory seems weakly supported by experimental studies since they are limited in number, show inconsistent results, do not include control conditions. We tested the response to a stressful task in smokers under abstinence and under no abstinence to verify if tobacco abstinence reduces task persistence, thus distress tolerance. A placebo-controlled, double-blind, randomized, cross-over design was used. Twenty smokers underwent a breath holding test after the administration of nicotine on one test day and a placebo on another test day. Physiological and psychological variables were assessed at baseline and directly before and after each challenge. Abstinence induced a statistically significant shorter breath holding duration relative to the nicotine condition. No different response to the breath holding test was observed when nicotine and placebo conditions were compared. No response to the breath holding test was found when pre- and post-test values of heart rate, blood pressure, Visual Analogue Scale for fear or discomfort were compared. In brief, tobacco abstinence reduces breath holding duration but breath holding test does not influence discomfort. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The conditional indirect effect model of women's union participation: the moderating effect of perceived union tolerance for sexual harassment.

PubMed

Mellor, Steven; Golay, Leslie M

2014-01-01

We tested a theoretically trimmed model of union participation presented by Tetrick, Shore, McClurg, and Vandenberg (2007), in which perceived union instrumentality is expected to influence participation through perceived union support. This testing was accomplished as a precursor to testing a conditional indirect effect model of women's participation--in which perceived union tolerance for sexual harassment was expected to moderate the influence of perceived support on willingness to participate in union activities. In a sample of 326 women from multiple unions, we found support for the conditional model; the influence of perceived instrumentality on willingness to participate through perceived support was moderated by perceived tolerance for harassment; specifically, the influence through perceived support was weak when perceived tolerance was high. The implications of our results are discussed in reference to need support and women's participation.

Allergy test outcomes in patients self-reported as having penicillin allergy: Two-year experience.

PubMed

Meng, Juan; Thursfield, David; Lukawska, Joanna J

2016-09-01

Penicillin allergy is associated with increased antibiotic resistance and health care costs. However, most patients with self-reported penicillin allergy are not truly allergic. To summarize our experience with allergy tests in patients with a history of penicillin allergy and to compare them with the results of other groups. We retrospectively reviewed all patients with a suspected clinical history of penicillin allergy referred to the Drug Allergy Unit at University College London Hospital between March 2013 and June 2015. In total, 84 patients were reviewed. The index drugs included: unidentified penicillin (n = 44), amoxicillin (n = 17), amoxicillin-clavulanic acid (n = 13), flucloxacillin (n = 4), and other penicillins (ampicillin, benzylpenicillin, piperacillin-tazobactam; n = 7). Allergy diagnoses were confirmed in 24 patients (28.6%) (16 to penicillin, 3 to flucloxacillin, 5 to clavulanic acid). Twenty-two patients (91.7%) had allergy diagnosed by positive skin test results. Two patients (8.3%) developed IgE-mediated allergic symptoms during oral challenge (although the skin test results were negative). In vitro specific IgE test results for penicilloyl V, penicilloyl G, and amoxicilloyl were positive in 3 of 16 patients (18.8%). Moreover, reactions to cefuroxime were observed in 3 of 15 patients with penicillin allergy (20%). Selective clavulanic acid and flucloxacillin responders tolerated amoxicillin challenge. The interval between the index reaction and evaluation was shorter (P < .001), and the proportion of patients who could recall the name of the culprit drug was higher (P = .009) in the allergic group. Furthermore, histories of anaphylaxis (33.3%), urticaria, and/or angioedema (58.3%) were more common in the allergic group. Unspecified rashes (35.0%) and nonspecific symptoms (28.3%) predominated in the nonallergic group. Only 28.6% of patients with self-reported penicillin allergy were confirmed to be allergic. Importantly, when the index drug is amoxicillin-clavulanic acid or flucloxacillin, the patients may tolerate amoxicillin. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Time between the first and second operations for staged total knee arthroplasties when the interval is determined by the patient.

PubMed

Ishii, Yoshinori; Noguchi, Hideo; Takeda, Mitsuhiro; Sato, Junko; Toyabe, Shin-Ichi

2014-01-01

The purpose of this study was to evaluate the interval between the first and second operations for staged total knee arthroplasties (TKAs) in patients with bilateral knee osteoarthritis. Depending on satisfactory preoperative health status, the patients determined the timing of the second operation. We also analysed correlations between the interval and patient characteristics. Eighty-six patients with bilateral knee osteoarthritis were analysed. The mean follow-up time from the first TKA was 96 months. The side of the first TKA was chosen by the patients. The timing of the second TKA was determined by the patients, depending on their perceived ability to tolerate the additional pain and limitations to activities of daily living. The median interval between the first and second operations was 12.5 months, with a range of 2 to 113 months. In 43 (50%) patients, the interval was <12 months. There was no difference in the interval between females and males (p=0.861), and no correlation between the interval and body mass index or age. There was weak correlation between the year of the first TKA and the interval (R=-0.251, p=0.020), with the interval getting significantly shorter as the years progressed (p=0.032). The median interval between the first and second operations in patients who underwent staged TKAs for bilateral knee osteoarthritis was about 1 year. The results of the current study may help patients and physicians to plan effective treatment strategies for staged TKAs. Level II. Copyright © 2013 Elsevier B.V. All rights reserved.

Automating linear accelerator quality assurance.

PubMed

Eckhause, Tobias; Al-Hallaq, Hania; Ritter, Timothy; DeMarco, John; Farrey, Karl; Pawlicki, Todd; Kim, Gwe-Ya; Popple, Richard; Sharma, Vijeshwar; Perez, Mario; Park, SungYong; Booth, Jeremy T; Thorwarth, Ryan; Moran, Jean M

2015-10-01

The purpose of this study was 2-fold. One purpose was to develop an automated, streamlined quality assurance (QA) program for use by multiple centers. The second purpose was to evaluate machine performance over time for multiple centers using linear accelerator (Linac) log files and electronic portal images. The authors sought to evaluate variations in Linac performance to establish as a reference for other centers. The authors developed analytical software tools for a QA program using both log files and electronic portal imaging device (EPID) measurements. The first tool is a general analysis tool which can read and visually represent data in the log file. This tool, which can be used to automatically analyze patient treatment or QA log files, examines the files for Linac deviations which exceed thresholds. The second set of tools consists of a test suite of QA fields, a standard phantom, and software to collect information from the log files on deviations from the expected values. The test suite was designed to focus on the mechanical tests of the Linac to include jaw, MLC, and collimator positions during static, IMRT, and volumetric modulated arc therapy delivery. A consortium of eight institutions delivered the test suite at monthly or weekly intervals on each Linac using a standard phantom. The behavior of various components was analyzed for eight TrueBeam Linacs. For the EPID and trajectory log file analysis, all observed deviations which exceeded established thresholds for Linac behavior resulted in a beam hold off. In the absence of an interlock-triggering event, the maximum observed log file deviations between the expected and actual component positions (such as MLC leaves) varied from less than 1% to 26% of published tolerance thresholds. The maximum and standard deviations of the variations due to gantry sag, collimator angle, jaw position, and MLC positions are presented. Gantry sag among Linacs was 0.336 ± 0.072 mm. The standard deviation in MLC position, as determined by EPID measurements, across the consortium was 0.33 mm for IMRT fields. With respect to the log files, the deviations between expected and actual positions for parameters were small (<0.12 mm) for all Linacs. Considering both log files and EPID measurements, all parameters were well within published tolerance values. Variations in collimator angle, MLC position, and gantry sag were also evaluated for all Linacs. The performance of the TrueBeam Linac model was shown to be consistent based on automated analysis of trajectory log files and EPID images acquired during delivery of a standardized test suite. The results can be compared directly to tolerance thresholds. In addition, sharing of results from standard tests across institutions can facilitate the identification of QA process and Linac changes. These reference values are presented along with the standard deviation for common tests so that the test suite can be used by other centers to evaluate their Linac performance against those in this consortium.

FTMP - A highly reliable Fault-Tolerant Multiprocessor for aircraft

NASA Technical Reports Server (NTRS)

Hopkins, A. L., Jr.; Smith, T. B., III; Lala, J. H.

1978-01-01

The FTMP (Fault-Tolerant Multiprocessor) is a complex multiprocessor computer that employs a form of redundancy related to systems considered by Mathur (1971), in which each major module can substitute for any other module of the same type. Despite the conceptual simplicity of the redundancy form, the implementation has many intricacies owing partly to the low target failure rate, and partly to the difficulty of eliminating single-fault vulnerability. An extensive analysis of the computer through the use of such modeling techniques as Markov processes and combinatorial mathematics shows that for random hard faults the computer can meet its requirements. It is also shown that the maintenance scheduled at intervals of 200 hr or more can be adequate most of the time.

The Influence of Passive Acceleration and Exercise+Acceleration on Work Capacity and Orthostasis

NASA Technical Reports Server (NTRS)

Simonson, S. R.; Cowell, S. A.; Stocks, J. M.; Biagini, H. W.; Vener, J. M.; Evetts, S. N.; Bailey, K. N.; Evans, J.; Knapp, C.; Greenleaf, J. E.

1999-01-01

The losses of aerobic power and orthostatic tolerance are significant effects of manned C) spaceflight that can negatively impact crew health and safety. Daily acceleration and aerobic training may ameliorate these effects. To determine the influence of passive intermittent +Gz acceleration (PA) training and active acceleration + interval exercise (AE) training on work 0 0 capacity and the acute (1 min) response to 70 deg head-up tilt, 6 men (X-Bar SD: age, 33 +/- 6 y; height, 178.3 +/- 4.6 cm; mass, 86.3 +/- 6.6 kg) participated in two 3-wk training protocols. It was hypothesized that PA and AE training would improve orthostatic tolerance and that the addition of aerobic conditioning, would not alter this effect.

Fault tolerant and lifetime control architecture for autonomous vehicles

NASA Astrophysics Data System (ADS)

Bogdanov, Alexander; Chen, Yi-Liang; Sundareswaran, Venkataraman; Altshuler, Thomas

2008-04-01

Increased vehicle autonomy, survivability and utility can provide an unprecedented impact on mission success and are one of the most desirable improvements for modern autonomous vehicles. We propose a general architecture of intelligent resource allocation, reconfigurable control and system restructuring for autonomous vehicles. The architecture is based on fault-tolerant control and lifetime prediction principles, and it provides improved vehicle survivability, extended service intervals, greater operational autonomy through lower rate of time-critical mission failures and lesser dependence on supplies and maintenance. The architecture enables mission distribution, adaptation and execution constrained on vehicle and payload faults and desirable lifetime. The proposed architecture will allow managing missions more efficiently by weighing vehicle capabilities versus mission objectives and replacing the vehicle only when it is necessary.

Reputation-Based Investment Helps to Optimize Group Behaviors in Spatial Lattice Networks.

PubMed

Ding, Hong; Cao, Lin; Ren, Yizhi; Choo, Kim-Kwang Raymond; Shi, Benyun

2016-01-01

Encouraging cooperation among selfish individuals is crucial in many real-world systems, where individuals' collective behaviors can be analyzed using evolutionary public goods game. Along this line, extensive studies have shown that reputation is an effective mechanism to investigate the evolution of cooperation. In most existing studies, participating individuals in a public goods game are assumed to contribute unconditionally into the public pool, or they can choose partners based on a common reputation standard (e.g., preferences or characters). However, to assign one reputation standard for all individuals is impractical in many real-world deployment. In this paper, we introduce a reputation tolerance mechanism that allows an individual to select its potential partners and decide whether or not to contribute an investment to the public pool based on its tolerance to other individuals' reputation. Specifically, an individual takes part in a public goods game only if the number of participants with higher reputation exceeds the value of its tolerance. Moreover, in this paper, an individual's reputation can increase or decrease in a bounded interval based on its historical behaviors. We explore the principle that how the reputation tolerance and conditional investment mechanisms can affect the evolution of cooperation in spatial lattice networks. Our simulation results demonstrate that a larger tolerance value can achieve an environment that promote the cooperation of participants.

Bowel cleansing before colonoscopy: Balancing efficacy, safety, cost and patient tolerance

PubMed Central

Harrison, Nicole M; Hjelkrem, Michael C

2016-01-01

Effective colorectal cancer screening relies on reliable colonoscopy findings which are themselves dependent on adequate bowel cleansing. Research has consistently demonstrated that inadequate bowel preparation adversely affects the adenoma detection rate and leads gastroenterologists to recommend earlier follow up than is consistent with published guidelines. Poor preparation affects as many as 30% of colonoscopies and contributes to an increased cost of colonoscopies. Patient tolerability is strongly affected by the preparation chosen and manner in which it is administered. Poor tolerability is, in turn, associated with lower quality bowel preparations. Recently, several new developments in both agents being used for bowel preparation and in the timing of administration have brought endoscopists closer to achieving the goal of effective, reliable, safe, and tolerable regimens. Historically, large volume preparations given in a single dose were administered to patients in order to achieve adequate bowel cleansing. These were poorly tolerated, and the unpleasant taste of and significant side effects produced by these large volume regimens contributed significantly to patients’ inability to reliably complete the preparation and to a reluctance to repeat the procedure. Smaller volumes, including preparations that are administered as tablets to be consumed with water, given as split doses have significantly improved both the patient experience and efficacy, and an appreciation of the importance of the preparation to colonoscopy interval have produced additional cleansing. PMID:26788258

Gestational diabetes mellitus screening, management and outcomes in the Cook Islands.

PubMed

Aung, Yin Yin May; Sowter, Martin; Kenealy, Timothy; Herman, Josephine; Ekeroma, Alec

2015-04-17

To describe current practices for screening for gestational diabetes mellitus in the Cook Islands and consider the implications of alternative screening strategies. Eligible women had antenatal care from January 2009 to December 2012. A non-fasting 50 g glucose challenge between 24 and 28 weeks gestation (positive if 1-hour glucose greater than or equal to 7.8 mmol/L) was followed by a 75 g oral glucose tolerance test (gestational diabetes mellitus diagnosed if fasting glucose greater than or equal to 5.2 mmol/L or 2-hour glucose greater than or equal to 8.0 mmol/L; pregnancy impaired glucose tolerance if positive screen and negative diagnostic test). Uptake of the screening programme rose from 49.0% to 99.6% by the end of the study period. 646 women had a glucose challenge; for 186/646 (28.8%) the challenge was positive; 183 had an oral glucose tolerance test; 89/646 (13.8%) had pregnancy impaired glucose tolerance; 94/646 (13.9%) had gestational diabetes mellitus. Median maternal weight gain was 6 kg (gestational diabetes mellitus) and 10 kg (normal glucose tolerance); caesarean section rates were 25% and 11% respectively; baby birthweights were not significantly different. 59 women with gestational diabetes mellitus had a post-natal glucose tolerance test at their 6-week check and 21 (35.6%) had diabetes confirmed. The gestational diabetes mellitus screening programme has a high uptake and current management appears effective in reducing maternal and fetal weight gain. A proposed new screening programme is outlined.

Test and analysis results for composite transport fuselage and wing structures

NASA Technical Reports Server (NTRS)

Deaton, Jerry W.; Kullerd, Susan M.; Madan, Ram C.; Chen, Victor L.

1992-01-01

Automated tow placement (ATP) and stitching of dry textile composite preforms followed by resin transfer molding (RTM) are being investigated by researchers at NASA LaRC and Douglas Aircraft Company as cost-effective manufacturing processes for obtaining damage tolerant fuselage and wing structures for transport aircraft. The Douglas work is being performed under a NASA contract entitled 'Innovative Composites Aircraft Primary Structures (ICAPS)'. Data are presented in this paper to assess the damage tolerance of ATP and RTM fuselage elements with stitched-on stiffeners from compression tests of impacted three-J-stiffened panels and from stiffener pull-off tests. Data are also presented to assess the damage tolerance of RTM wing elements which had stitched skin and stiffeners from impacted single stiffener and three blade-stiffened compression tests and stiffener pull-off tests.

Low velocity instrumented impact testing of four new damage tolerant carbon/epoxy composite systems

NASA Technical Reports Server (NTRS)

Lance, D. G.; Nettles, A. T.

1990-01-01

Low velocity drop weight instrumented impact testing was utilized to examine the damage resistance of four recently developed carbon fiber/epoxy resin systems. A fifth material, T300/934, for which a large data base exists, was also tested for comparison purposes. A 16-ply quasi-isotropic lay-up configuration was used for all the specimens. Force/absorbed energy-time plots were generated for each impact test. The specimens were cross-sectionally analyzed to record the damage corresponding to each impact energy level. Maximum force of impact versus impact energy plots were constructed to compare the various systems for impact damage resistance. Results show that the four new damage tolerant fiber/resin systems far outclassed the T300/934 material. The most damage tolerant material tested was the IM7/1962 fiber/resin system.

Opioid tolerance and urine drug testing among initiates of extended-release or long-acting opioids in Food and Drug Administration's Sentinel System.

PubMed

Larochelle, Marc R; Cocoros, Noelle M; Popovic, Jennifer; Dee, Elizabeth C; Kornegay, Cynthia; Ju, Jing; Racoosin, Judith A

A risk evaluation and mitigation strategy for extended-release and long-acting (ER/LA) opioid analgesics was approved by the Food and Drug Administration in 2012. Our objective was to assess frequency of opioid tolerance and urine drug testing for individuals initiating ER/LA opioid analgesics. Retrospective cohort study. Sentinel, a distributed database with electronic healthcare data on >190 million predominantly commercially insured members. Members under age 65 initiating ER/LA opioid analgesics between January 2009 and December 2013. We examined the proportion of opioid-tolerant-only ER/LA opioid analgesic initiates meeting tolerance criteria: receipt of ≥30 mg oxycodone equivalents per day in 7 days prior to the first opioid-tolerant-only dispensing. We separately examined the proportion of new users of extended-release oxycodone (ERO) and other ER/LA opioid analgesics with a claim for a urine drug test in the 30 days prior to, and separately for the 183 days after, dispensing. We identified 79,824 ERO, 7,343 extended-release hydromorphone, and 91,778 transdermal fentanyl opi-oid-tolerant-only episodes. Tolerance criteria were met in 64 percent of ERO, 64 percent of extended-release hydromorphone and 40 percent of transdermal fentanyl episodes. We identified 210,581 incident ERO and 311,660 other ER/LA opioid analgesic episodes. Use of urine drug testing for ERO compared with other ER/LA opioid analgesics was: 4 percent vs 14 percent respectively in the 30 days prior to initiation and 9 percent vs 23 percent respectively in the 183 days following initiation. These results suggest potential areas for improving appropriate ER/LA opioid analgesic prescribing practices.

Impaired glucose tolerance in patients with amyotrophic lateral sclerosis.

PubMed

Pradat, Pierre-Francois; Bruneteau, Gaelle; Gordon, Paul H; Dupuis, Luc; Bonnefont-Rousselot, Dominique; Simon, Dominique; Salachas, Francois; Corcia, Philippe; Frochot, Vincent; Lacorte, Jean-Marc; Jardel, Claude; Coussieu, Christiane; Le Forestier, Nadine; Lacomblez, Lucette; Loeffler, Jean-Philippe; Meininger, Vincent

2010-01-01

Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.

40 CFR 172.3 - Scope of requirement.

Code of Federal Regulations, 2010 CFR

2010-07-01

... experimental use permit (EUP) is generally required for testing of any unregistered pesticide or any registered... testing for more than one target pest occurs at the same time and in the same locality, the 10 acre... experimental animals unless an appropriate tolerance or exemption from a tolerance has been established under...

40 CFR 172.3 - Scope of requirement.

Code of Federal Regulations, 2012 CFR

2012-07-01

... experimental use permit (EUP) is generally required for testing of any unregistered pesticide or any registered... testing for more than one target pest occurs at the same time and in the same locality, the 10 acre... experimental animals unless an appropriate tolerance or exemption from a tolerance has been established under...

Advanced information processing system - Status report. [for fault tolerant and damage tolerant data processing for aerospace vehicles

NASA Technical Reports Server (NTRS)

Brock, L. D.; Lala, J.

1986-01-01

The Advanced Information Processing System (AIPS) is designed to provide a fault tolerant and damage tolerant data processing architecture for a broad range of aerospace vehicles. The AIPS architecture also has attributes to enhance system effectiveness such as graceful degradation, growth and change tolerance, integrability, etc. Two key building blocks being developed by the AIPS program are a fault and damage tolerant processor and communication network. A proof-of-concept system is now being built and will be tested to demonstrate the validity and performance of the AIPS concepts.

A novel system for in situ determination of heat tolerance of plants: first results on alpine dwarf shrubs

PubMed Central

2013-01-01

Background Heat stress and heat damage to plants gain globally increasing importance for crop production and plant survival in endangered habitats. Therefore the knowledge of heat tolerance of plants is of great interest. As many heat tolerance measurement procedures require detachment of plants and protocols expose samples to various heat temperatures in darkness, the ecological relevance of such results may be doubted. To overcome these constraints we designed a novel field compatible Heat Tolerance Testing System (HTTS) that opens the opportunity to induce controlled heat stress on plants in situ under full natural solar irradiation. Subsequently, heat tolerance can be evaluated by a variety of standard viability assays like the electrolyte leakage test, chlorophyll fluorescence measurements and visual assessment methods. Furthermore, recuperation can be studied under natural environmental conditions which is impossible when detached plant material is used. First results obtained on three alpine dwarf - shrubs are presented. Results When heat tolerance of Vaccinium gaultherioides Bigelow was tested with the HTTS in situ, the visual assessment of leaves showed 50% heat injury (LT50) at 48.3°C, while on detached leaves where heat exposure took place in small heat chambers this already happened at 45.8°C. Natural solar irradiation being applied during heat exposure in the HTTS had significantly protective effects: In Loiseleuria procumbens L. (Desv.), if heat exposure (in situ) took place in darkness, leaf heat tolerance was 50.6°C. In contrast, when heat exposure was conducted under full natural solar irradiation heat tolerance was increased to 53.1°C. In Rhododendron ferrugineum L. heat tolerance of leaves was 42.5°C if the exposure took place ex situ and in darkness, while it was significantly increased to 45.8°C when this happened in situ under natural solar irradiation. Conclusions The results obtained with the HTTS tested in the field indicate a mitigating effect of natural solar irradiation during heat exposure. Commonly used laboratory based measurement procedures expose samples in darkness and seem to underestimate leaf heat tolerance. Avoidance of detachment by the use of the HTTS allows studying heat tolerance and recuperation processes in the presence of interacting external abiotic, biotic and genetic factors under field conditions. The investigation of combined effects of heat exposure under full solar irradiation, of recuperation and repair processes but also of possible damage amplification into the results with the HTTS appears to be particularly useful as it allows determining heat tolerance of plants with a considerably high ecological significance. PMID:23497517

Tolerability of loteprednol/tobramycin versus dexamethasone/tobramycin in healthy volunteers: results of a 4-week, randomized, double-masked, parallel-group study.

PubMed

Bartlett, Jimmy D; Holland, Edward J; Usner, Dale W; Paterno, Michael R; Comstock, Timothy L

2008-08-01

To compare the ocular comfort and tolerability of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; TobraDex) in healthy volunteers. In this multicenter, randomized, double-masked, parallel-group study, healthy volunteers (n = 306) were randomized to receive LE/T or DM/T four times per day for 28 days. Subjects recorded subjective ratings for seven comfort/tolerability parameters using an electronic patient diary (EPD). The primary endpoint was the difference at week 4 from the ratings of an artificial tear at baseline in comfort/tolerability parameters between treatment groups, using a noninferiority paradigm. ClinicalTrials. gov, NCT 00532961. The 97.5% confidence intervals for the lower bound were within -10 for all of the seven comfort/ tolerability parameters evaluated (pain, stinging/burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity). Secondary analysis revealed small but significant within-treatment differences in pain favoring LE/T over tears and in light sensitivity favoring tears over DM/T (p < 0.01). Small between-treatment differences in the changes from baseline tear ratings to individual study visits favored LE/T for pain, stinging/burning, irritation, itchiness, foreign-body sensation, and light sensitivity at visit 4 (p < or = 0.04); for pain, stinging/burning, and foreignbody sensation at visit 5 (p < or = 0.03), and for dryness and light sensitivity at visit 6 (p < or = 0.05). LE/T satisfied all conditions of noninferiority to DM/T in comfort and tolerability. Subjects receiving LE/T were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T. The study population consisted of healthy volunteers.

Anti-A2 and anti-A1 domain antibodies are potential predictors of immune tolerance induction outcome in children with hemophilia A.

PubMed

Lapalud, P; Rothschild, C; Mathieu-Dupas, E; Balicchi, J; Gruel, Y; Laune, D; Molina, F; Schved, J F; Granier, C; Lavigne-Lissalde, G

2015-04-01

Hemophilia A (HA) is a congenital bleeding disorder resulting from factor VIII deficiency. The most serious complication of HA management is the appearance of inhibitory antibodies (Abs) against injected FVIII concentrates. To eradicate inhibitors, immune tolerance induction (ITI) is usually attempted, but it fails in up to 30% of cases. Currently, no undisputed predictive marker of ITI outcome is available to facilitate the clinical decision. To identify predictive markers of ITI efficacy. The isotypic and epitopic repertoires of inhibitory Abs were analyzed in plasma samples collected before ITI initiation from 15 children with severe HA and high-titer inhibitors, and their levels were compared in the two outcome groups (ITI success [n = 7] and ITI failure [n = 8]). The predictive value of these candidate biomarkers and of the currently used indicators (inhibitor titer and age at ITI initiation, highest inhibitor titer before ITI, and interval between inhibitor diagnosis and ITI initiation) was then compared by statistical analysis (Wilcoxon test and receiver receiver operating characteristic [ROC] curve analysis). Whereas current indicators seemed to fail in discriminating patients in the two outcome groups (ITI success or failure), anti-A1 and anti-A2 Ab levels before ITI initiation appeared to be good potential predictive markers of ITI outcome (P < 0.018). ROC analysis showed that anti-A1 and anti-A2 Abs were the best at discriminating between outcome groups (area under the ROC curve of > 0.875). Anti-A1 and anti-A2 Abs could represent new promising tools for the development of ITI outcome prediction tests for children with severe HA. © 2015 International Society on Thrombosis and Haemostasis.

Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency.

PubMed

Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B; Enns, Gregory M; Jones, Simon A; Kane, John P; Stock, Eveline O; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A; Sharma, Reena; Twelves, Chris; Whitley, Chester B; Quinn, Anthony G

2014-11-01

Lysosomal acid lipase deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Sebelipase alfa (1mg/kg or 3mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. 216 infusions were administered to eight adult subjects through week 52 during LAL-CL04. At week 52, mean alanine aminotransferase and aspartate aminotransferase levels were normal with mean change from baseline of -58% and -40%. Mean changes for low-density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were -60%, -39%, -36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of a hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Long-term dosing with sebelipase alfa in lysosomal acid lipase-deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in the hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A prospective observational study of the relationship of critical illness associated hyperglycaemia in medical ICU patients and subsequent development of type 2 diabetes

PubMed Central

2010-01-01

Introduction Critical illness is commonly complicated by hyperglycaemia caused by mediators of stress and inflammation. Severity of disease is the main risk factor for development of hyperglycaemia, but not all severely ill develop hyperglycemia and some do even in mild disease. We hypothesised that acute disease only exposes a latent disturbance of glucose metabolism which puts those patients at higher risk for developing diabetes. Methods Medical patients with no history of impaired glucose metabolism or other endocrine disorder admitted to an intensive care unit between July 1998 and June 2004 were considered for inclusion. Glucose was measured at least two times a day, and patients were divided into the hyperglycaemia group (glucose ≥7.8 mmol/l) and normoglycaemia group. An oral glucose tolerance test was performed within six weeks after discharge to disclose patients with unknown diabetes or pre-diabetes who were excluded. Patients treated with corticosteroids and those terminally ill were also excluded from the follow-up which lasted for a minimum of five years with annual oral glucose tolerance tests. Results A five-year follow-up was completed for 398 patients in the normoglycaemia group, of which 14 (3.5%) developed type 2 diabetes. In the hyperglycaemia group 193 patients finished follow-up and 33 (17.1%) developed type 2 diabetes. The relative risk for type 2 diabetes during five years after the acute illness was 5.6 (95% confidence interval (CI) 3.1 to 10.2). Conclusions Patients with hyperglycaemia during acute illness who are not diagnosed with diabetes before or during the hospitalization should be considered a population at increased risk for developing diabetes. They should, therefore, be followed-up, in order to be timely diagnosed and treated. PMID:20615210

Sebelipase alfa over 52 weeks reduces serum transaminases, liver volume and improves serum lipids in patients with lysosomal acid lipase deficiency

PubMed Central

Valayannopoulos, Vassili; Malinova, Vera; Honzík, Tomas; Balwani, Manisha; Breen, Catherine; Deegan, Patrick B.; Enns, Gregory M.; Jones, Simon A.; Kane, John P.; Stock, Eveline O.; Tripuraneni, Radhika; Eckert, Stephen; Schneider, Eugene; Hamilton, Gavin; Middleton, Michael S.; Sirlin, Claude; Kessler, Bruce; Bourdon, Christopher; Boyadjiev, Simeon A.; Sharma, Reena; Twelves, Chris; Whitley, Chester B.; Quinn, Anthony G.

2014-01-01

Background and aims Lysosomal Acid Lipase Deficiency is an autosomal recessive enzyme deficiency resulting in lysosomal accumulation of cholesteryl esters and triglycerides. LAL-CL04, an ongoing extension study, investigates the long-term effects of sebelipase alfa, a recombinant human lysosomal acid lipase. Methods Sebelipase alfa (1 mg/kg or 3 mg/kg) was infused every-other-week to eligible subjects. Safety and tolerability assessments, including liver function, lipid profiles and liver volume assessment, were carried out at regular intervals. Results 216 infusions were administered to eight adult subjects through Week 52 during LAL-CL04. At Week 52, mean alanine aminotransferase and aspartate aminotransferase were normal with mean change from baseline of −58% and −40%. Mean change for low density lipoprotein, total cholesterol, triglyceride and high-density lipoprotein were −60%, −39%, −36%, and +29%, respectively. Mean liver volume by magnetic resonance imaging and hepatic proton density fat fraction decreased (12% and 55%, respectively). Adverse events were mainly mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon: three events of moderate severity were reported in two subjects; one patient's event was suggestive of hypersensitivity-like reaction, but additional testing did not confirm this, and the subject has successfully re-started sebelipase alfa. Of samples tested to date, no anti-drug antibodies have been detected. Conclusions Long-term dosing with sebelipase alfa in Lysosomal Acid Lipase-Deficient patients is well tolerated and produces sustained reductions in transaminases, improvements in serum lipid profile and reduction in hepatic fat fraction. A randomized, placebo-controlled phase 3 trial in children and adults is underway (ARISE: NCT01757184). PMID:24993530

[Indicators of dynamic work tolerability in healthy subjects].

PubMed

Capodaglio, E M; Capodaglio, P

1997-01-01

This paper reports a study on the dynamics of tolerability in performing dynamic cycling in healthy subjects. Data on individually tolerable levels (power x duration) was obtained from 9 subjects by means of three submaximal tests on an ergometric bicycle lasting < or = 40 minutes, with constant load (50%, 65% and 80% of maximum VO2 reached during a previous test of increasing difficulty within the limits of the symptoms). During performance of the test we monitored heart rate and subjective perception of fatigue (Borg's 10-point scale). We then defined the individual functions of "isoperception", which expressed the individual trend of the product "power x duration" at identical subjective perception score. On the basis of the metabolic parameters monitored, the individual isoperceptive functions at a "moderate" level of fatigue (3 on the Borg scale) were defined as "tolerability) threshold" for prolonged dynamic cycling. The product "power x duration" defined by the isoperceptive curves at a "moderate" level of fatigue does in fact reflect the individual aerobic capacity that can be sustained for prolonged dynamic activity (under 60 minutes). In order to validate the hypothesis of tolerability of the functions identified, three further short tests were performed (duration < or = 8.5 minutes) on an ergometric bicycle, with measurement of ventilatory and metabolic parameters.

Modeling and Simulation Reliable Spacecraft On-Board Computing

NASA Technical Reports Server (NTRS)

Park, Nohpill

1999-01-01

The proposed project will investigate modeling and simulation-driven testing and fault tolerance schemes for Spacecraft On-Board Computing, thereby achieving reliable spacecraft telecommunication. A spacecraft communication system has inherent capabilities of providing multipoint and broadcast transmission, connectivity between any two distant nodes within a wide-area coverage, quick network configuration /reconfiguration, rapid allocation of space segment capacity, and distance-insensitive cost. To realize the capabilities above mentioned, both the size and cost of the ground-station terminals have to be reduced by using reliable, high-throughput, fast and cost-effective on-board computing system which has been known to be a critical contributor to the overall performance of space mission deployment. Controlled vulnerability of mission data (measured in sensitivity), improved performance (measured in throughput and delay) and fault tolerance (measured in reliability) are some of the most important features of these systems. The system should be thoroughly tested and diagnosed before employing a fault tolerance into the system. Testing and fault tolerance strategies should be driven by accurate performance models (i.e. throughput, delay, reliability and sensitivity) to find an optimal solution in terms of reliability and cost. The modeling and simulation tools will be integrated with a system architecture module, a testing module and a module for fault tolerance all of which interacting through a centered graphical user interface.

Tolerability of aztreonam and carbapenems in patients with IgE-mediated hypersensitivity to penicillins.

PubMed

Gaeta, Francesco; Valluzzi, Rocco Luigi; Alonzi, Cristiana; Maggioletti, Michela; Caruso, Cristiano; Romano, Antonino

2015-04-01

Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Development of Murine Lupus Involves the Combined Genetic Contribution of the SLAM and FcγR Intervals within the Nba2 Autoimmune Susceptibility Locus

PubMed Central

Jørgensen, Trine N.; Alfaro, Jennifer; Enriquez, Hilda L.; Jiang, Chao; Loo, William M.; Atencio, Stephanie; Bupp, Melanie R. Gubbels; Mailloux, Christina M.; Metzger, Troy; Flannery, Shannon; Rozzo, Stephen J.; Kotzin, Brian L.; Rosemblatt, Mario; Bono, María Rosa; Erickson, Loren D.

2010-01-01

Autoantibodies are of central importance in the pathogenesis of Ab-mediated autoimmune disorders. The murine lupus susceptibility locus Nba2 on chromosome 1 and the syntenic human locus are associated with a loss of immune tolerance that leads to antinuclear Ab production. To identify gene intervals within Nba2 that control the development of autoantibody-producing B cells and to determine the cellular components through which Nba2 genes accomplish this, we generated congenic mice expressing various Nba2 intervals where genes for the FcγR, SLAM, and IFN-inducible families are encoded. Analysis of congenic strains demonstrated that the FcγR and SLAM intervals independently controlled the severity of autoantibody production and renal disease, yet are both required for lupus susceptibility. Deregulated homeostasis of terminally differentiated B cells was found to be controlled by the FcγR interval where FcγRIIb-mediated apoptosis of germinal center B cells and plasma cells was impaired. Increased numbers of activated plasmacytoid dendritic cells that were distinctly CD19+ and promoted plasma cell differentiation via the proinflammatory cytokines IL-10 and IFNα were linked to the SLAM interval. These findings suggest that SLAM and FcγR intervals act cooperatively to influence the clinical course of disease through supporting the differentiation and survival of autoantibody-producing cells. PMID:20018631

Chronic voluntary alcohol consumption results in tolerance to sedative/hypnotic and hypothermic effects of alcohol in hybrid mice

PubMed Central

Ozburn, Angela Renee; Harris, R. Adron; Blednov, Yuri A.

2013-01-01

The continuous two bottle choice test is the most common measure of alcohol consumption but there is remarkably little information about the development of tolerance or dependence with this procedure. We showed that C57BL/6JxFVB/NJ and FVB/NJxC57BL/6J F1 hybrid mice demonstrate greater preference for and consumption of alcohol than either parental strain. In order to test the ability of this genetic model of high alcohol consumption to produce neuroadaptation, we examined development of alcohol tolerance and dependence after chronic self-administration using a continuous access two-bottle choice paradigm. Ethanol-experienced mice stably consumed about 16–18 g/kg/day of ethanol. Ethanol-induced withdrawal severity was assessed (after 59 days of drinking) by scoring handling-induced convulsions; withdrawal severity was minimal and did not differ between ethanol-experienced and -naïve mice. After 71 days of drinking, the rate of ethanol clearance was similar for ethanol-experienced and -naïve mice. After 77 days of drinking, ethanol-induced loss of righting reflex (LORR) was tested daily for 5 days. Ethanol-experienced mice had a shorter duration of LORR. For both ethanol-experienced and -naïve mice, blood ethanol concentrations taken at gain of righting reflex were greater on day 5 than on day 1, indicative of tolerance. After 98 days of drinking, ethanol-induced hypothermia was assessed daily for 3 days. Both ethanol-experienced and –naïve mice developed rapid and chronic tolerance to ethanol-induced hypothermia, with significant group differences on the first day of testing. In summary, chronic, high levels of alcohol consumption in F1 hybrid mice produced rapid and chronic tolerance to both the sedative/hypnotic and hypothermic effects of ethanol; additionally, a small degree of metabolic tolerance developed. The development of tolerance supports the validity of using this model of high alcohol consumption in genetic studies of alcoholism. PMID:23313769

Validation of antibiotic residue tests for dairy goats.

PubMed

Zeng, S S; Hart, S; Escobar, E N; Tesfai, K

1998-03-01

The SNAP test, LacTek test (B-L and CEF), Charm Bacillus sterothermophilus var. calidolactis disk assay (BsDA), and Charm II Tablet Beta-lactam sequential test were validated using antibiotic-fortified and -incurred goat milk following the protocol for test kit validations of the U.S. Food and Drug Administration Center for Veterinary Medicine. SNAP, Charm BsDA, and Charm II Tablet Sequential tests were sensitive and reliable in detecting antibiotic residues in goat milk. All three assays showed greater than 90% sensitivity and specificity at tolerance and detection levels. However, caution should be taken in interpreting test results at detection levels. Because of the high sensitivity of these three tests, false-violative results could be obtained in goat milk containing antibiotic residues below the tolerance level. Goat milk testing positive by these tests must be confirmed using a more sophisticated methodology, such as high-performance liquid chromatography, before the milk is condemned. LacTek B-L test did not detect several antibiotics, including penicillin G, in goat milk at tolerance levels. However, LacTek CEF was excellent in detecting ceftiofur residue in goat milk.

Basal measures of insulin sensitivity and insulin secretion and simplified glucose tolerance tests in dogs.

PubMed

Verkest, K R; Fleeman, L M; Rand, J S; Morton, J M

2010-10-01

There is need for simple, inexpensive measures of glucose tolerance, insulin sensitivity, and insulin secretion in dogs. The aim of this study was to estimate the closeness of correlation between fasting and dynamic measures of insulin sensitivity and insulin secretion, the precision of fasting measures, and the agreement between results of standard and simplified glucose tolerance tests in dogs. A retrospective descriptive study using 6 naturally occurring obese and 6 lean dogs was conducted. Data from frequently sampled intravenous glucose tolerance tests (FSIGTTs) in 6 obese and 6 lean client-owned dogs were used to calculate HOMA, QUICKI, fasting glucose and insulin concentrations. Fasting measures of insulin sensitivity and secretion were compared with MINMOD analysis of FSIGTTs using Pearson correlation coefficients, and they were evaluated for precision by the discriminant ratio. Simplified sampling protocols were compared with standard FSIGTTs using Lin's concordance correlation coefficients, limits of agreement, and Pearson correlation coefficients. All fasting measures except fasting plasma glucose concentration were moderately correlated with MINMOD-estimated insulin sensitivity (|r| = 0.62-0.80; P < 0.03), and those that combined fasting insulin and glucose were moderately closely correlated with MINMOD-estimated insulin secretion (r = 0.60-0.79; P < 0.04). HOMA calculated using the nonlinear formulae had the closest estimated correlation (r = 0.77 and 0.74) and the best discrimination for insulin sensitivity and insulin secretion (discriminant ratio 4.4 and 3.4, respectively). Simplified sampling protocols with half as many samples collected over 3 h had close agreement with the full sampling protocol. Fasting measures and simplified intravenous glucose tolerance tests reflect insulin sensitivity and insulin secretion derived from frequently sampled glucose tolerance tests with MINMOD analysis in dogs. Copyright 2010 Elsevier Inc. All rights reserved.

Development and Event-specific Detection of Transgenic Glyphosate-resistant Rice Expressing the G2-EPSPS Gene

PubMed Central

Dong, Yufeng; Jin, Xi; Tang, Qiaoling; Zhang, Xin; Yang, Jiangtao; Liu, Xiaojing; Cai, Junfeng; Zhang, Xiaobing; Wang, Xujing; Wang, Zhixing

2017-01-01

Glyphosate is a widely used herbicide, due to its broad spectrum, low cost, low toxicity, high efficiency, and non-selective characteristics. Rice farmers rarely use glyphosate as a herbicide, because the crop is sensitive to this chemical. The development of transgenic glyphosate-tolerant rice could greatly improve the economics of rice production. Here, we transformed the Pseudomonas fluorescens G2 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS) gene G2-EPSPS, which conferred tolerance to glyphosate herbicide into a widely used japonica rice cultivar, Zhonghua 11 (ZH11), to develop two highly glyphosate-tolerant transgenic rice lines, G2-6 and G2-7, with one exogenous gene integration. Seed germination tests and glyphosate-tolerance assays of plants grown in a greenhouse showed that the two transgenic lines could greatly improve glyphosate-tolerance compared with the wild-type; The glyphosate-tolerance field test indicated that both transgenic lines could grow at concentrations of 20,000 ppm glyphosate, which is more than 20-times the recommended concentration in the field. Isolation of the flanking sequence of transgenic rice G2-6 indicated that the 5′-terminal of T-DNA was inserted into chromosome 8 of the rice genome. An event-specific PCR test system was established and the limit of detection of the primers reached five copies. Overall, the G2-EPSPS gene significantly improved glyphosate-tolerance in transgenic rice; furthermore, it is a useful candidate gene for the future development of commercial transgenic rice. PMID:28611804

7 CFR 801.12 - Design requirements incorporated by reference.

Code of Federal Regulations, 2010 CFR

2010-01-01

... reference: General Code (1.10.) G-S.5.5. Money Values, Mathematical Agreement G-T.1. Acceptance Tolerances G.... Tolerance Values T.3. For Test Weight Per Bushel Indications or Recorded Representations UR.3.2. Other... Standards and Technology's (NIST) Handbook 44, “Specifications, Tolerances, and Other Technical Requirements...

Fuel Cycle Research and Development Accident Tolerant Fuels Series 1 (ATF-1) Irradiation Testing FY 2016 Status Report

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

Core, Gregory Matthew

This report contains a summary of irradiation testing of Fuel Cycle Research and Development (FCRD) Accident Tolerant Fuels Series 1 (ATF 1) experiments performed at Idaho National Laboratory (INL) in FY 2016. ATF 1 irradiation testing work performed in FY 2016 included design, analysis, and fabrication of ATF-1B drop in capsule ATF 1 series experiments and irradiation testing of ATF-1 capsules in the ATR.

Prioritization of Candidate Genes in QTL Regions for Physiological and Biochemical Traits Underlying Drought Response in Barley (Hordeum vulgare L.)

PubMed Central

Gudys, Kornelia; Guzy-Wrobelska, Justyna; Janiak, Agnieszka; Dziurka, Michał A.; Ostrowska, Agnieszka; Hura, Katarzyna; Jurczyk, Barbara; Żmuda, Katarzyna; Grzybkowska, Daria; Śróbka, Joanna; Urban, Wojciech; Biesaga-Koscielniak, Jolanta; Filek, Maria; Koscielniak, Janusz; Mikołajczak, Krzysztof; Ogrodowicz, Piotr; Krystkowiak, Karolina; Kuczyńska, Anetta; Krajewski, Paweł; Szarejko, Iwona

2018-01-01

Drought is one of the most adverse abiotic factors limiting growth and productivity of crops. Among them is barley, ranked fourth cereal worldwide in terms of harvested acreage and production. Plants have evolved various mechanisms to cope with water deficit at different biological levels, but there is an enormous challenge to decipher genes responsible for particular complex phenotypic traits, in order to develop drought tolerant crops. This work presents a comprehensive approach for elucidation of molecular mechanisms of drought tolerance in barley at the seedling stage of development. The study includes mapping of QTLs for physiological and biochemical traits associated with drought tolerance on a high-density function map, projection of QTL confidence intervals on barley physical map, and the retrievement of positional candidate genes (CGs), followed by their prioritization based on Gene Ontology (GO) enrichment analysis. A total of 64 QTLs for 25 physiological and biochemical traits that describe plant water status, photosynthetic efficiency, osmoprotectant and hormone content, as well as antioxidant activity, were positioned on a consensus map, constructed using RIL populations developed from the crosses between European and Syrian genotypes. The map contained a total of 875 SNP, SSR and CGs, spanning 941.86 cM with resolution of 1.1 cM. For the first time, QTLs for ethylene, glucose, sucrose, maltose, raffinose, α-tocopherol, γ-tocotrienol content, and catalase activity, have been mapped in barley. Based on overlapping confidence intervals of QTLs, 11 hotspots were identified that enclosed more than 60% of mapped QTLs. Genetic and physical map integration allowed the identification of 1,101 positional CGs within the confidence intervals of drought response-specific QTLs. Prioritization resulted in the designation of 143 CGs, among them were genes encoding antioxidants, carboxylic acid biosynthesis enzymes, heat shock proteins, small auxin up-regulated RNAs, nitric oxide synthase, ATP sulfurylases, and proteins involved in regulation of flowering time. This global approach may be proposed for identification of new CGs that underlies QTLs responsible for complex traits. PMID:29946328

Anti-nociceptive interactions between opioids and a cannabinoid receptor 2 agonist in inflammatory pain

PubMed Central

Hale, David E; Guindon, Josée; Morgan, Daniel J

2017-01-01

The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain. The low level of adverse side effects and lack of tolerance for cannabinoid 2 receptor agonists are attractive pharmacotherapeutic traits. This study assessed the anti-nociceptive effects of a selective cannabinoid 2 receptor agonist (JWH-133) in pathological pain using mice subjected to inflammatory pain using the formalin test. Furthermore, we examined several ways in which JWH-133 may interact with morphine. JWH-133 produces dose-dependent anti-nociception during both the acute and inflammatory phases of the formalin test. This was observed in both male and female mice. However, a maximally efficacious dose of JWH-133 (1 mg/kg) was not associated with somatic withdrawal symptoms, motor impairment, or hypothermia. After eleven once-daily injections of 1 mg/JWH-133, no tolerance was observed in the formalin test. Cross-tolerance for the anti-nociceptive effects of JWH-133 and morphine were assessed to gain insight into physiologically relevant cannabinoid 2 receptor and mu-opioid receptor interaction. Mice made tolerant to the effects of morphine exhibited a lower JWH-133 response in both phases of the formalin test compared to vehicle-treated morphine-naïve animals. However, repeated daily JWH-133 administration did not cause cross-tolerance for morphine, suggesting opioid and cannabinoid 2 receptor cross-tolerance is unidirectional. However, preliminary data suggest co-administration of JWH-133 with morphine modestly attenuates morphine tolerance. Isobolographic analysis revealed that co-administration of JWH-133 and morphine has an additive effect on anti-nociception in the formalin test. Overall these findings show that cannabinoid 2 receptor may functionally interact with mu-opioid receptor to modulate anti-nociception in the formalin test. PMID:28879802

Relative bioavailability of generic and branded acetylcysteine effervescent tablets: A single-dose, open-label, randomized-sequence, two-period crossover study in fasting healthy Chinese male volunteers.

PubMed

Liu, Yan-Mei; Liu, Yun; Lu, Chuan; Jia, Jing-Ying; Liu, Gang-Yi; Weng, Li-Ping; Wang, Jia-Yan; Li, Guo-Xiu; Wang, Wei; Li, Shui-Jun; Yu, Chen

2010-11-01

Acetylcysteine may be used as a muco- lytic agent for the treatment of chronic bronchitis, chronic obstructive pulmonary disease, and other pulmonary diseases complicated by the production of viscous mucus. However, little is known of its pharmacokinetic properties when given orally in healthy volunteers, particularly in a Chinese Han population. This study was conducted to provide support for the marketing of a generic product in China. The purpose of this study was to compare the pharmacokinetics and relative bioavailability of a generic test formulation and a branded reference formulation of acetylcysteine in fasting healthy Chinese male volunteers. A single-dose, open-label, randomized-sequence, 2-period crossover design with a 7-day washout period between doses was used in this study. Healthy Chinese male nonsmokers aged 18 to 40 years with a body mass index (BMI) of 19 to 25 kg/m(2) were selected. Eligible volunteers were randomly assigned to receive acetylcysteine 600 mg PO as either the test formulation (3 tablets of 200 mg each) or reference formulation (1 tablet of 600 mg) under fasting conditions. A total of 15 serial blood samples were collected over a 24-hour interval, and total plasma acetylcysteine concentrations were analyzed by a validated liquid chromatography-isotopic dilution mass spectrometry method. Pharmacokinetic parameters (C(max), T(max), t(½) AUC(0-t), and AUC(0-∞) were calculated and analyzed statistically. The 2 formulations were considered bioequivalent if the 90% CIs of the log-transformed ratios (test/reference) of C(max) and AUC were within the predetermined bioequivalence ranges (70%-143% for C(max); 80%-125% for AUC), as established by the State Food and Drug Administration of China. Tolerability was determined by vital signs, clinical laboratory tests, 12-lead ECGs, physical examinations, and interviews with the subjects about adverse events (AEs). A total of 24 healthy Chinese Han male volunteers were enrolled in and completed the study (mean [SD] age, 25.0 [2.4] years; height, 173.0 [5.6] cm; weight, 65.9 [6.4] kg; BMI, 22.0 [1.7] kg/m(2)). No formulation, period, or sequence effects were observed. The 90% CIs for the log-transformed C(max), AUC(0-t), and AUC(0-∞) were 89.7% to 103.8%, 86.7% to 101.7%, and 87.7% to 102.4%, respectively, which met the predetermined criteria for assuming bioequivalence. Two subjects (8.3%) experienced 2 mild AEs (increase in total bile acid and prolongation of the QT interval), which were not considered to be related to study drug administration. This single-dose study of acetylcysteine 600 mg PO found that the 3 tablets of the generic test formulation and 1 tablet of the branded reference formulation met the regulatory criteria for assuming bioequivalence in these fasting healthy Chinese male volunteers. Both formulations were generally well tolerated.

The Role of the Environment in the Evolution of Tolerance and Resistance to a Pathogen.

PubMed

Zeller, Michael; Koella, Jacob C

2017-09-01

Defense against parasites can be divided into resistance, which limits parasite burden, and tolerance, which reduces pathogenesis at a given parasite burden. Distinguishing between the two and understanding which defense is favored by evolution in different ecological settings are important, as they lead to fundamentally different evolutionary trajectories of host-parasite interactions. We let the mosquito Aedes aegypti evolve under different food levels and with either no parasite, a constant parasite, or a coevolving parasite (the microsporidian Vavraia culicis). We then tested tolerance and resistance of the evolved lines on a population level at the two food levels. Exposure to parasites during evolution increased resistance and tolerance, but there were no differences between the lines evolved with coevolving or constant parasites. Mosquitoes that had evolved with food restriction had higher resistance than those evolved with high food but similar tolerance. The mosquitoes that had restricted food when being tested had lower tolerance than those with normal food, but there was no difference in resistance. Our results emphasize the complexity and dependence on environmental conditions of the evolution and expression of resistance and tolerance and help to evaluate some of the predictions about the evolution of host defense against parasites.

Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase.

PubMed

Marcus, David J; Zee, Michael; Hughes, Alex; Yuill, Matthew B; Hohmann, Andrea G; Mackie, Ken; Guindon, Josée; Morgan, Daniel J

2015-06-12

Morphine and fentanyl are opioid analgesics in wide clinical use that act through the μ-opioid receptor (MOR). However, one limitation of their long-term effectiveness is the development of tolerance. Receptor desensitization has been proposed as a putative mechanism driving tolerance to G protein-coupled receptor (GPCR) agonists. Recent studies have found that tolerance to morphine is mediated by the c-Jun N-terminal Kinase (JNK) signaling pathway. The goal of the present study was to test the hypotheses that: 1) JNK inhibition will be antinociceptive on its own; 2) JNK inhibition will augment morphine antinociception and; 3) JNK mediates chronic tolerance for the antinociceptive effects of morphine using acute (hotplate and tail-flick), inflammatory (10 μl of formalin 2.5%) and chemotherapy (cisplatin 5 mg/kg ip once weekly)-induced neuropathic pain assays. We found that JNK inhibition by SP600125 (3 mg/kg) produces a greater antinociceptive effect than morphine (6 mg/kg) alone in the formalin test. Moreover, co-administration of morphine (6 mg/kg) with SP600125 (3 mg/kg) produced a sub-additive antinociceptive effect in the formalin test. We also show that pre-treatment with SP600125 (3 or 10 mg/kg), attenuates tolerance to the antinociceptive effects of morphine (10 mg/kg), but not fentanyl (0.3 mg/kg), in the tail-flick and hotplate tests. Pre-treatment with SP600125 also attenuates tolerance to the hypothermic effects of both morphine and fentanyl. We also examined the role of JNK in morphine tolerance in a cisplatin-induced model of neuropathic pain. Interestingly, treatment with SP600125 (3 mg/kg) alone attenuated mechanical and cold allodynia in a chemotherapy-induced pain model using cisplatin. Strikingly, SP600125 (3 mg/kg) pre-treatment prolonged the anti-allodynic effect of morphine by several days (5 and 7 days for mechanical and cold, respectively). These results demonstrate that JNK signaling plays a crucial role in mediating antinociception as well as chronic tolerance to the antinociceptive effects of morphine in acute, inflammatory, and neuropathic pain states. Thus, inhibition of JNK signaling pathway, via SP600125, represents an efficacious pharmacological approach to delay tolerance to the antinociceptive effects of chronic morphine in diverse pain models.

In polycystic ovary syndrome, adrenal steroids are regulated differently in the morning versus in response to nutrient intake

USDA-ARS?s Scientific Manuscript database

The objective of this study was to investigate adrenal steroid regulation in Polycystic Ovary Syndrome (PCOS). A 5-h oral glucose tolerance test (OGTT) and a 3-h frequently sampled-intravenous glucose tolerance test (FSIVGTT) were administered to 30 patients with PCOS. Anthropometric parameters (hei...

PRN 2007-2: Guidance on Small-Scale Field Testing and Low-level Presence in Food of Plant-Incorporated Protectants (PIPs)

EPA Pesticide Factsheets

This notice clarifies how EPA ensures the safety of residues of PIPs possibly present in food or feed and when a tolerance or tolerance exemption would be required for field tests for biotechnology-derived food and feed crop plants containing PIPs.

Confidence Intervals for Weighted Composite Scores under the Compound Binomial Error Model

ERIC Educational Resources Information Center

Kim, Kyung Yong; Lee, Won-Chan

2018-01-01

Reporting confidence intervals with test scores helps test users make important decisions about examinees by providing information about the precision of test scores. Although a variety of estimation procedures based on the binomial error model are available for computing intervals for test scores, these procedures assume that items are randomly…

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

PubMed Central

Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

2015-01-01

Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

Likelihood of myocardial infarction during stroke rehabilitation preceded by cardiovascular screening and an exercise tolerance test: the Locomotor Experience Applied Post-Stroke (LEAPS) trial.

PubMed

Nadeau, Stephen E; Rose, Dorian Kay; Dobkin, Bruce; Wu, Samuel S; Dai, Yufeng E; Schofield, Richard; Duncan, Pamela W

2014-12-01

Coronary artery disease is highly prevalent in patients with stroke, but because revascularization does not improve major clinical outcomes in patients with stable coronary artery disease relative to intensive medical therapy, routine evaluation for this disease is not warranted in stroke patients. However, it might be warranted in patients destined to undergo vigorous physical therapy. The Locomotor Experience Applied Post-Stroke study, a randomized controlled trial of 408 participants that tested the relative efficacy of two rehabilitation techniques on functional walking level, provided the opportunity to address this question. The study aims to test the efficacy of screening for cardiovascular disease and an exercise tolerance test in assuring safety among patients undergoing vigorous rehabilitation for gait impairment. All participants were screened for serious cardiovascular and pulmonary conditions. At six-weeks poststroke, they also completed a cardiovascular screening inventory and underwent an exercise tolerance test involving bicycle ergometry. Participants received 36, 90-min sessions of a prescribed physical therapy (three per week), initiated at either two-months or six-months poststroke. Twenty-nine participants were excluded on the basis of the cardiac screening questionnaire, and 15 failed the exercise tolerance test for cardiovascular reasons. No participant experienced a cardiac event during a treatment session. Two participants experienced myocardial infarctions, but continued in the trial. In three additional participants, myocardial infarctions caused or contributed to death. The combination of a negative cardiac screen and the absence of exercise tolerance test failure appeared to have a high negative predictive value for cardiac events during treatment, despite the likelihood of a high prevalence of coronary artery disease in our population. © 2014 World Stroke Organization.

Optimized lower leg injury probability curves from postmortem human subject tests under axial impacts.

PubMed

Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A; Szabo, Aniko

2014-01-01

Derive optimum injury probability curves to describe human tolerance of the lower leg using parametric survival analysis. The study reexamined lower leg postmortem human subjects (PMHS) data from a large group of specimens. Briefly, axial loading experiments were conducted by impacting the plantar surface of the foot. Both injury and noninjury tests were included in the testing process. They were identified by pre- and posttest radiographic images and detailed dissection following the impact test. Fractures included injuries to the calcaneus and distal tibia-fibula complex (including pylon), representing severities at the Abbreviated Injury Score (AIS) level 2+. For the statistical analysis, peak force was chosen as the main explanatory variable and the age was chosen as the covariable. Censoring statuses depended on experimental outcomes. Parameters from the parametric survival analysis were estimated using the maximum likelihood approach and the dfbetas statistic was used to identify overly influential samples. The best fit from the Weibull, log-normal, and log-logistic distributions was based on the Akaike information criterion. Plus and minus 95% confidence intervals were obtained for the optimum injury probability distribution. The relative sizes of the interval were determined at predetermined risk levels. Quality indices were described at each of the selected probability levels. The mean age, stature, and weight were 58.2±15.1 years, 1.74±0.08 m, and 74.9±13.8 kg, respectively. Excluding all overly influential tests resulted in the tightest confidence intervals. The Weibull distribution was the most optimum function compared to the other 2 distributions. A majority of quality indices were in the good category for this optimum distribution when results were extracted for 25-, 45- and 65-year-olds at 5, 25, and 50% risk levels age groups for lower leg fracture. For 25, 45, and 65 years, peak forces were 8.1, 6.5, and 5.1 kN at 5% risk; 9.6, 7.7, and 6.1 kN at 25% risk; and 10.4, 8.3, and 6.6 kN at 50% risk, respectively. This study derived axial loading-induced injury risk curves based on survival analysis using peak force and specimen age; adopting different censoring schemes; considering overly influential samples in the analysis; and assessing the quality of the distribution at discrete probability levels. Because procedures used in the present survival analysis are accepted by international automotive communities, current optimum human injury probability distributions can be used at all risk levels with more confidence in future crashworthiness applications for automotive and other disciplines.

Fasting capillary blood glucose: an appropriate measurement in screening for diabetes and pre-diabetes in low-resource rural settings.

PubMed

Zhao, X; Zhao, W; Zhang, H; Li, J; Shu, Y; Li, S; Cai, L; Zhou, J; Li, Y; Hu, R

2013-01-01

To evaluate the efficiency of fasting capillary blood glucose (FCG) measurement as compared with fasting venous plasma glucose (FPG) measurement in screening diabetes and pre-diabetes in low-resource rural settings. In 2010, 993 participants were randomly selected from 9 villages in Yunnan province using cluster sampling method. Samples for FCG and FPG test were obtained after demographics and physical examination. The oral glucose tolerance test was performed in parallel as gold standard for diagnosis. Diagnostic capacities of the FCG measurement in predicting undiagnosed diabetes and pre-diabetes were assessed. The performance of FCG and FPG tests was compared. Fifty-seven individuals with undiagnosed diabetes and 145 subjects with pre-diabetes were detected. The concordance between FCG and FPG levels was high (r = 0.75, p < 0.001). The area under the curve (AUC) for FCG test in predicting diabetes was 0.88 [95% confidence interval (CI) 0.82-0.93] with the optimal cutoff value of 5.65 mmol/l, sensitivity of 84.2%, and specificity of 79.3%. The corresponding values in FPG tests were 0.92 (95% CI 0.88-0.97) (AUC), 6.51 mmol/l (optimal cutoff point), 82.5% (sensitivity) and 98.3% (specificity), respectively. No significant difference was found in the AUC for the two screening strategies. FCG measurement is considered to be a convenient, practicable screening method in low-resource rural communities with acceptable test properties.

Normative values for a tablet computer-based application to assess chromatic contrast sensitivity.

PubMed

Bodduluri, Lakshmi; Boon, Mei Ying; Ryan, Malcolm; Dain, Stephen J

2018-04-01

Tablet computer displays are amenable for the development of vision tests in a portable form. Assessing color vision using an easily accessible and portable test may help in the self-monitoring of vision-related changes in ocular/systemic conditions and assist in the early detection of disease processes. Tablet computer-based games were developed with different levels of gamification as a more portable option to assess chromatic contrast sensitivity. Game 1 was designed as a clinical version with no gaming elements. Game 2 was a gamified version of game 1 (added fun elements: feedback, scores, and sounds) and game 3 was a complete game with vision task nested within. The current study aimed to determine the normative values and evaluate repeatability of the tablet computer-based games in comparison with an established test, the Cambridge Colour Test (CCT) Trivector test. Normally sighted individuals [N = 100, median (range) age 19.0 years (18-56 years)] had their chromatic contrast sensitivity evaluated binocularly using the three games and the CCT. Games 1 and 2 and the CCT showed similar absolute thresholds and tolerance intervals, and game 3 had significantly lower values than games 1, 2, and the CCT, due to visual task differences. With the exception of game 3 for blue-yellow, the CCT and tablet computer-based games showed similar repeatability with comparable 95% limits of agreement. The custom-designed games are portable, rapid, and may find application in routine clinical practice, especially for testing younger populations.

The DIAMIND study: postpartum SMS reminders to women who have had gestational diabetes mellitus to test for type 2 diabetes: a randomised controlled trial - study protocol.

PubMed

Heatley, Emer; Middleton, Philippa; Hague, William; Crowther, Caroline

2013-04-12

Postpartum follow up of women who have been found to have gestational diabetes during pregnancy is essential because of the strong association of gestational diabetes with subsequent type 2 diabetes. Postal reminders have been shown to increase significantly attendance for oral glucose tolerance testing postpartum. It is possible that a short message service (text) reminder system may also be effective. This trial aims to assess whether a text message reminder system for women who have experienced gestational diabetes in their index pregnancy will increase attendance for oral glucose tolerance testing within six months after birth. Single centre (Women's and Children's Hospital, South Australia), parallel group randomised controlled trial. Women diagnosed with gestational diabetes in their index pregnancy (oral glucose tolerance test with fasting glucose ≥ 5.5 mmol/L and/or two hour glucose ≥ 7.8 mmol/L), with access to a mobile phone, whose capillary blood glucose profile measurements prior to postnatal discharge are all normal (fasting glucose < 6.0 mmol/L, postprandial glucoses < 8.0 mmol/L). Pregestational diabetes mellitus, triplet/higher order multiple birth or stillbirth in the index pregnancy, requirement for interpreter.Trial entry and randomisation: Allocation to intervention will be undertaken using a telephone randomisation service (computer-generated random number sequence generation, with balanced variable blocks, and stratification by insulin requirement).Study groups: Women in the intervention group will receive a text reminder to attend for an oral glucose tolerance test at 6 weeks postpartum, with further reminders at 3 months and 6 months if they do not respond to indicate test completion. Women in the control group will receive a single text message reminder at 6 months postpartum.Blinding: Baseline data collection will be undertaken blinded. Blinding of participants and blinded collection of primary outcome data will not be possible for this study.Primary study outcome: Attendance for the oral glucose tolerance test within 6 months postpartum. 276 subjects will be required to show an 18% absolute increase in the rate of attendance (α=0.05 two tailed, β=80%, 5% loss to follow up) from 37% to 55% in the intervention group. Given the heightened risk of impaired glucose tolerance and type 2 diabetes in women who have had gestational diabetes, ensuring the highest possible rate of attendance for postpartum glucose tolerance testing, so that early diagnosis and intervention can occur, is important. A text message reminder system may prove to be an effective method for achieving improved attendance for such testing. This randomised controlled trial will assess whether such a system will increase rates of attendance for postpartum oral glucose tolerance testing in women who have experienced gestational diabetes. Australian New Zealand Clinical Trials Registry - ACTRN12612000621819.

Phase I/II randomized trial of aerobic exercise in Parkinson disease in a community setting.

PubMed

Uc, Ergun Y; Doerschug, Kevin C; Magnotta, Vincent; Dawson, Jeffrey D; Thomsen, Teri R; Kline, Joel N; Rizzo, Matthew; Newman, Sara R; Mehta, Sonya; Grabowski, Thomas J; Bruss, Joel; Blanchette, Derek R; Anderson, Steven W; Voss, Michelle W; Kramer, Arthur F; Darling, Warren G

2014-07-29

To (1) investigate effects of aerobic walking on motor function, cognition, and quality of life in Parkinson disease (PD), and (2) compare safety, tolerability, and fitness benefits of different forms of exercise intervention: continuous/moderate intensity vs interval/alternating between low and vigorous intensity, and individual/neighborhood vs group/facility setting. Initial design was a 6-month, 2 × 2 randomized trial of different exercise regimens in independently ambulatory patients with PD. All arms were required to exercise 3 times per week, 45 minutes per session. Randomization to group/facility setting was not feasible because of logistical factors. Over the first 2 years, we randomized 43 participants to continuous or interval training. Because preliminary analyses suggested higher musculoskeletal adverse events in the interval group and lack of difference between training methods in improving fitness, the next 17 participants were allocated only to continuous training. Eighty-one percent of 60 participants completed the study with a mean attendance of 83.3% (95% confidence interval: 77.5%-89.0%), exercising at 46.8% (44.0%-49.7%) of their heart rate reserve. There were no serious adverse events. Across all completers, we observed improvements in maximum oxygen consumption, gait speed, Unified Parkinson's Disease Rating Scale sections I and III scores (particularly axial functions and rigidity), fatigue, depression, quality of life (e.g., psychological outlook), and flanker task scores (p < 0.05 to p < 0.001). Increase in maximum oxygen consumption correlated with improvements on the flanker task and quality of life (p < 0.05). Our preliminary study suggests that aerobic walking in a community setting is safe, well tolerated, and improves aerobic fitness, motor function, fatigue, mood, executive control, and quality of life in mild to moderate PD. This study provides Class IV evidence that in patients with PD, an aerobic exercise program improves aerobic fitness, motor function, fatigue, mood, and cognition. © 2014 American Academy of Neurology.

Shuttle filter study. Volume 3: Appendix

NASA Technical Reports Server (NTRS)

1974-01-01

Test data obtained from flow resistance and contaminant tolerance tests on the various porous media evaluated in the different fluids are presented in both graphical and tabular forms. Test procedures for both flow resistance and contaminant tolerance testing are presented, and the development of a system for continuously adding contaminant at a predetermined rate to a flowing fluid stream is described. Also included is a section describing the development effort of the self-indexing filter. This concept was adapted during this program for various shuttle applications.

The DPP-4 inhibitor linagliptin does not prolong the QT interval at therapeutic and supratherapeutic doses

PubMed Central

Ring, Arne; Port, Andreas; Graefe-Mody, E Ulrike; Revollo, Ivette; Iovino, Mario; Dugi, Klaus A

2011-01-01

AIM To evaluate the potential effects of therapeutic and supratherapeutic doses of linagliptin (BI 1356) on the QT/QTc interval in healthy subjects. METHODS The study was a randomized, double-blind, placebo-controlled, four-period crossover study using single oral doses of linagliptin (5 mg and 100 mg), moxifloxacin (400 mg) and placebo. Electrocardiogram (ECG) profiles using triplicates of 12-lead 10-s ECGs were digitally recorded pre-dose and after drug administration. The mean change from baseline (MCfB) of the individually heart rate corrected QT interval (QTcI) between 1 and 4 h postdrug administration was the primary end point. Blood samples to measure plasma concentrations of linagliptin and its main metabolite were also obtained. RESULTS Forty-four Caucasian subjects (26 male) entered the study and 43 subjects completed the study as planned in the protocol. Linagliptin was not associated with an increase in the baseline-adjusted mean QTcI, at any time point. The placebo-corrected MCfB of QTcI was −1.1 (90% CI −2.7, 0.5) ms and −2.5 (–4.1, –0.9) ms for linagliptin 5 mg and 100 mg, respectively, thus within the non-inferiority margin of 10 ms according to ICH E14. Linagliptin was well tolerated; the assessment of ECGs and other safety parameters gave no clinically relevant findings at either dose tested. Maximum plasma concentrations after administration of 100-mg linagliptin were ∼24-fold higher than those observed previously for chronic treatment with the therapeutic 5-mg dose. Assay sensitivity was confirmed by a placebo-corrected MCfB of QTcI with moxifloxacin of 6.9 (90% CI 5.4, 8.5) ms. CONCLUSIONS Therapeutic and significantly supratherapeutic exposure to linagliptin is not associated with QT interval prolongation. PMID:21306414

pH tolerance in freshwater bacterioplankton: trait variation of the community as measured by leucine incorporation.

PubMed

Bååth, Erland; Kritzberg, Emma

2015-11-01

pH is an important factor determining bacterial community composition in soil and water. We have directly determined the community tolerance (trait variation) to pH in communities from 22 lakes and streams ranging in pH from 4 to 9 using a growth-based method not relying on distinguishing between individual populations. The pH in the water samples was altered to up to 16 pH values, covering in situ pH ± 2.5 U, and the tolerance was assessed by measuring bacterial growth (Leu incorporation) instantaneously after pH adjustment. The resulting unimodal response curves, reflecting community tolerance to pH, were well modeled with a double logistic equation (mean R(2) = 0.97). The optimal pH for growth (pHopt) among the bacterial communities was closely correlated with in situ pH, with a slope (0.89 ± 0.099) close to unity. The pH interval, in which growth was ≥90% of that at pHopt, was 1.1 to 3 pH units wide (mean 2.0 pH units). Tolerance response curves of communities originating from circum-neutral pH were symmetrical, whereas in high-pH (8.9) and especially in low-pH (<5.5) waters, asymmetric tolerance curves were found. In low-pH waters, decreasing pH was more detrimental for bacterial growth than increasing pH, with a tendency for the opposite for high-pH waters. A pH tolerance index, using the ratio of growth at only two pH values (pH 4 and 8), was closely related to pHopt (R(2) = 0.83), allowing for easy determination of pH tolerance during rapid changes in pH. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Management Strategies for Statin-Associated Muscle Symptoms: How Useful Is Same-Statin Rechallenge?

PubMed

Brennan, Emily T; Joy, Tisha R

2017-05-01

Statin-associated muscle symptoms (SAMS) are common. Rechallenge with the same statin (same-statin rechallenge) has recently been included as part of a proposed scoring index for diagnosing SAMS, but data regarding tolerability and efficacy of same-statin rechallenge, compared with other strategies, is minimal. In this study we evaluated the tolerability, percent change in low-density lipoprotein cholesterol (LDL-C), and proportion of patients achieving their LDL-C targets among 3 common management strategies-same-statin rechallenge, switching to a different statin (statin switch), and use of nonstatin medications only. We performed a retrospective analysis of 118 patients referred to our tertiary care centre for management of SAMS, defined as development of muscle-related symptoms with 2 or more statins. Baseline and last follow-up lipid parameters were documented. Patients were classified as tolerant of a strategy if, at their last follow-up, they remained on that strategy. After a median follow-up of 17 months, most (n = 79; 67%) patients were able to tolerate a statin. Tolerability was similar among the 3 treatment strategies (71% same-statin rechallenge vs 53% statin switch vs 57% for nonstatin therapy only; P = 0.11). Those in the same-statin rechallenge and statin switch groups achieved greater LDL-C reductions compared with those who only tolerated nonstatins (-38.8 ± 3.4% vs -36.4 ± 2.9% vs -17.3 ± 4.5%; P = 0.0007). A greater proportion of patients in the same-statin rechallenge group achieved their target LDL-C compared with those in the nonstatin therapy only group (50% vs 15%; odds ratio, 6.8; 95% confidence interval, 1.5-40.7; P = 0.04). Among individuals with a history of SAMS, most will tolerate statin therapy. Same-statin rechallenge was highly tolerable and efficacious. Thus, same-statin rechallenge might warrant increased utilization. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin.

PubMed

Eastwood, S V; Tillin, T; Mayet, J; Shibata, D K; Wright, A; Heasman, J; Beauchamp, N; Forouhi, N G; Hughes, A D; Chaturvedi, N

2016-03-01

We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. For 682 European and 520 South Asian men and women, aged 58-85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist-hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c -defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c -defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Zero Tolerance: Don't Be a Square!

ERIC Educational Resources Information Center

Warren, Thomas P.; Rich, Wesley D.; Townsend, Megan; Mohrbutter, Trent L.; Brinson, Kenneth H.

2010-01-01

At Wentworth, rule violations are normally minor in nature and handled at the private school administration's discretion. A recent event involving the possession and use of alcohol during an off-campus school overnight activity leads to the development of a zero tolerance substance abuse policy. The zero tolerance policy is tested by one of the…

Directionality between Tolerance of Deviance and Deviant Behavior Is Age-Moderated in Chronically Stressed Youth

ERIC Educational Resources Information Center

Ridenour, Ty A.; Caldwell, Linda L.; Coatsworth, J. Douglas; Gold, Melanie A.

2011-01-01

Problem behavior theory posits that tolerance of deviance is an antecedent to antisocial behavior and substance use. In contrast, cognitive dissonance theory implies that acceptability of a behavior may increase after experiencing the behavior. Using structural equation modeling, this investigation tested whether changes in tolerance of deviance…

Reducing the width of confidence intervals for the difference between two population means by inverting adaptive tests.

PubMed

O'Gorman, Thomas W

2018-05-01

In the last decade, it has been shown that an adaptive testing method could be used, along with the Robbins-Monro search procedure, to obtain confidence intervals that are often narrower than traditional confidence intervals. However, these confidence interval limits require a great deal of computation and some familiarity with stochastic search methods. We propose a method for estimating the limits of confidence intervals that uses only a few tests of significance. We compare these limits to those obtained by a lengthy Robbins-Monro stochastic search and find that the proposed method is nearly as accurate as the Robbins-Monro search. Adaptive confidence intervals that are produced by the proposed method are often narrower than traditional confidence intervals when the distributions are long-tailed, skewed, or bimodal. Moreover, the proposed method of estimating confidence interval limits is easy to understand, because it is based solely on the p-values from a few tests of significance.

Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients.

PubMed

Martínez-Llordella, Marc; Lozano, Juan José; Puig-Pey, Isabel; Orlando, Giuseppe; Tisone, Giuseppe; Lerut, Jan; Benítez, Carlos; Pons, Jose Antonio; Parrilla, Pascual; Ramírez, Pablo; Bruguera, Miquel; Rimola, Antoni; Sánchez-Fueyo, Alberto

2008-08-01

A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.

Identification of Rhizobium phaseoli Strains That Are Tolerant or Sensitive to Soil Acidity

PubMed Central

Lowendorf, Henry S.; Alexander, Martin

1983-01-01

A study was conducted to determine whether the survival of Rhizobium phaseoli in acid soils could be predicted on the basis of the tolerance of the organism to acidity in culture. Of 16 strains tested, all grew in culture at pH 4.6, but only those that grew at pH 3.8 survived in soils having pH values of 4.1 to 4.6. Strains that tolerated the lowest pH values in culture were tolerant of the highest aluminum concentrations. In one acid soil, an acid-tolerant strain was unable to survive in numbers greater than 100/g, but the poor survival was not related to the level of extractable aluminum or manganese in the soil. Reproduction of an acid-tolerant strain of R. phaseoli was enhanced in the rhizosphere of Phaseolus vulgaris in both acid and limed soils, but stimulation of an acid-sensitive strain by the plant occurred only in the limed soil. These results indicate that cultural tests can be used to predict the ability of R. phaseoli to survive in acid soil. PMID:16346239

Temperature responses of tropical to warm temperate Cladophora species in relation to their distribution in the North Atlantic Ocean

NASA Astrophysics Data System (ADS)

Cambridge, M. L.; Breeman, A. M.; Kraak, S.; van den Hoek, C.

1987-09-01

The relationship between distribution boundaries and temperature responses of some North Atlantic Cladophora species (Chlorophyta) was experimentally examined under various regimes of temperature, light and daylength. Experimentally determined critical temperature intervals, in which survival, growth or reproduction was limited, were compared with annual temperature regimes (monthly means and extremes) at sites inside and outside distribution boundaries. The species tested belonged to two phytogeographic groups: (1) the tropical West Atlantic group ( C. submarina: isolate from Curaçao) and (2) the amphiatlantic tropical to warm temperate group ( C. prolifera: isolate from Corsica; C. coelothrix: isolates from Brittany and Curaçao; and C. laetevirens: isolates from deep and shallow water in Corsica and from Brittany). In accordance with distribution from tropical to warm temperate regions, each of the species grew well between 20 30°C and reproduction and growth were limited at and below 15°C. The upper survival limit in long days was <35°C in all species but high or maximum growth rates occurred at 30°C. C. prolifera, restricted to the tropical margins, had the most limited survival at 35°C. Experimental evidence suggests that C. submarina is restricted to the Caribbean and excluded from the more northerly American mainland and Gulf of Mexico coasts by sporadic low winter temperatures in the nearshore waters, when cold northerly weather penetrates far south every few years. Experimental evidence suggests that C. prolifera, C. coelothrix and C. laetevirens are restricted to their northern European boundaries by summer temperatures too low for sufficient growth and/or reproduction. Their progressively more northerly located boundaries were accounted for by differences in growth rates over the critical 10 15°C interval. C. prolifera and C. coelothrix are excluded or restricted in distribution on North Sea coasts by lethal winter temperatures, again differences in cold tolerance accounting for differences in their distribution patterns. On the American coast, species were probably restricted by lethal winter temperatures in the nearshore and, in some cases, by the absence of suitable hard substrates in the more equable offshore waters. Isolates from two points along the European coast (Brittany, Corsica) of C. laetevirens showed no marked differences in their temperature tolerance but the Caribbean and European isolates of C. coelothrix differed markedly in their tolerance to low temperatures, the lethal limit of the Caribbean isolate lying more than 5°C higher (at ca 5°C).

Processing of silicon solar cells by ion implantation and laser annealing

NASA Technical Reports Server (NTRS)

Minnucci, J. A.; Matthei, K. W.; Greenwald, A. C.

1981-01-01

Methods to improve the radiation tolerance of silicon cells for spacecraft use are described. The major emphasis of the program was to reduce the process-induced carbon and oxygen impurities in the junction and base regions of the solar cell, and to measure the effect of reduced impurity levels on the radiation tolerance of cells. Substrates of 0.1, 1.0 and 10.0 ohm-cm float-zone material were used as starting material in the process sequence. High-dose, low-energy ion implantation was used to form the junction in n+p structures. Implant annealing was performed by conventional furnace techniques and by pulsed laser and pulsed electron beam annealing. Cells were tested for radiation tolerance at Spire and NASA-LeRC. After irradiation by 1 MeV electrons to a fluence of 10 to the 16th power per sq cm, the cells tested at Spire showed no significant process induced variations in radiation tolerance. However, for cells tested at Lewis to a fluence of 10 to the 15th power per sq cm, ion-implanted cells annealed in vacuum by pulsed electron beam consistently showed the best radiation tolerance for all cell resistivities.

The effects of interval- vs. continuous exercise on excess post-exercise oxygen consumption and substrate oxidation rates in subjects with type 2 diabetes.

PubMed

Karstoft, Kristian; Wallis, Gareth A; Pedersen, Bente K; Solomon, Thomas P J

2016-09-01

For unknown reasons, interval training often reduces body weight more than energy-expenditure matched continuous training. We compared the acute effects of time-duration and oxygen-consumption matched interval- vs. continuous exercise on excess post-exercise oxygen consumption (EPOC), substrate oxidation rates and lipid metabolism in the hours following exercise in subjects with type 2 diabetes (T2D). Following an overnight fast, ten T2D subjects (M/F: 7/3; age=60.3±2.3years; body mass index (BMI)=28.3±1.1kg/m(2)) completed three 60-min interventions in a counterbalanced, randomized order: 1) control (CON), 2) continuous walking (CW), 3) interval-walking (IW - repeated cycles of 3min of fast and 3min of slow walking). Indirect calorimetry was applied during each intervention and repeatedly for 30min per hour during the following 5h. A liquid mixed meal tolerance test (MMTT, 450kcal) was consumed by the subjects 45min after completion of the intervention with blood samples taken regularly. Exercise interventions were successfully matched for total oxygen consumption (CW=1641±133mL/min; IW=1634±126mL/min, P>0.05). EPOC was higher after IW (8.4±1.3l) compared to CW (3.7±1.4l, P<0.05). Lipid oxidation rates were increased during the MMTT in IW (1.03±0.12mg/kg per min) and CW (0.87±0.04mg/kg per min) compared with CON (0.73±0.04mg/kg per min, P<0.01 and P<0.05, respectively), with no difference between IW and CW. Moreover, free fatty acids and glycerol concentrations, and glycerol kinetics were increased comparably during and after IW and CW compared to CON. Interval exercise results in greater EPOC than oxygen-consumption matched continuous exercise during a post-exercise MMTT in subjects with T2D, whereas effects on substrate oxidation and lipid metabolism are comparable. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-F-T-313: Clinical Results of a New Customer Acceptance Test for Elekta VMAT

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

Rusk, B; Fontenot, J

Purpose: To report the results of a customer acceptance test (CAT) for VMAT treatments for two matched Elekta linear accelerators. Methods: The CAT tests were performed on two clinically matched Elekta linear accelerators equipped with a 160-leaf MLC. Functional tests included performance checks of the control system during dynamic movements of the diaphragms, MLC, and gantry. Dosimetric tests included MLC picket fence tests at static and variable dose rates and a diaphragm alignment test, all performed using the on-board EPID. Additionally, beam symmetry during arc delivery was measured at the four cardinal angles for high and low dose rate modesmore » using a 2D detector array. Results of the dosimetric tests were analyzed using the VMAT CAT analysis tool. Results: Linear accelerator 1 (LN1) met all stated CAT tolerances. Linear accelerator 2 (LN2) passed the geometric, beam symmetry, and MLC position error tests but failed the relative dose average test for the diaphragm abutment and all three picket fence fields. Though peak doses in the abutment regions were consistent, the average dose was below the stated tolerance corresponding to a leaf junction that was too narrow. Despite this, no significant differences in patient specific VMAT quality assurance measured were observed between the accelerators and both passed monthly MLC quality assurance performed with the Hancock test. Conclusion: Results from the CAT showed LN2 with relative dose averages in the abutment regions of the diaphragm and MLC tests outside the tolerances resulting from differences in leaf gap distances. Tolerances of the dose average tests from the CAT may be small enough to detect MLC errors which do not significantly affect patient QA or the routine MLC tests.« less

Tolerance and dose-volume relationship of intrathoracic stomach irradiation after esophagectomy for patients with thoracic esophageal squamous cell carcinoma.

PubMed

Liu, Qi; Cai, Xu-Wei; Fu, Xiao-Long; Chen, Jun-Chao; Xiang, Jia-Qing

2015-10-13

To identify the tolerance of radiation with a high prescribed dose and predictors for the development of intrathoracic stomach toxicity in patients with thoracic esophageal squamous cell carcinoma (SCC) after esophagectomy followed by gastric conduit reconstruction. From 2011 to 2013, 105 patients after esophagectomy were treated with postoperative radiotherapy. The intrathoracic stomach was outlined with the calculation of a dose-volume histogram (DVH) for the initial intended treatment of 6020 cGy or 6300 cGy. The volume of the intrathoracic stomach receiving each dose was recorded at 10-Gy intervals between 10 and 40 Gy and at 5-Gy intervals between 40 and 60 Gy. The grade of toxicities was defined by the National Cancer Institute Common Toxicity Criteria version 4.0. The mean and maximum doses of the intrathoracic stomach were 2449 ± 986 cGy and 6519 ± 406 cGy, respectively. Sixteen (15.2%) and three (2.9%) experienced Common Toxicity Criteria Grade 2 and Grade 3 acute gastric toxicity. There were no Grade 4 toxicities. Fourteen patients (13.3%) exhibited late gastric complications possibly related to radiation. The volume percent of the intrathoracic stomach receiving at least 50 Gy (V50) was strongly associated with the degree of toxicity (p = 0.024, respectively). Multivariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicities. The intrathoracic stomach is well tolerated with a high-dose irradiation for patients with esophageal SCC receiving radiotherapy after esophagectomy. A strong dose-volume relationship exists for the development of Grade 2 acute intrathoracic stomach toxicity in our study.

Effectiveness of granisetron in controlling pediatric gastroenteritis-related vomiting after discharge from the ED.

PubMed

Qazi, Khajista; BinSalleeh, Hashim M; Shah, Ubaid H; AlGhamedi, Najwa; Tamim, Hani; Mubasher, Mohamed; Alrasheed, Faris; Alkanhal, Abdulrahman; AlTamimi, Saleh A

2014-09-01

The objective of the study is to determine the efficacy of oral granisetron (a long-acting 5-HT3 receptor antagonist) in stopping vomiting subsequent to discharge from emergency department (ED), in 6-month-old to 8-year-old patients with gastroenteritis-related vomiting and dehydration, who had failed an initial trial of oral rehydration (ORT). Eligible patients were offered ORT on a slowly advancing schedule. Patients who tolerated the initial ORT were discharged home. Patients who vomited were randomized to receive either 40 μg/kg of granisetron or placebo, and ORT was resumed. Patients who tolerated the postrandomization ORT were discharged home with another dose of the study drug. Parents were contacted by telephone every 24 hours until complete resolution of symptoms. The primary outcome was the proportion of patients with vomiting at 24 hours. Of the 900 eligible patients, 537 (60%) tolerated the initial ORT and were discharged home. Of the patients who vomited during the initial ORT, 165 were included in the final study sample (placebo, n = 82; granisetron, n = 83). There was no statistically significant difference in the proportion of patients with vomiting at 24 hours (granisetron, n = 38; placebo, n = 45; odds ratio, 0.64; 95% confidence interval, 0.34-1.19; P = .16). A similar trend in the proportion of patients with vomiting was noted for the entire follow-up period (granisetron, n = 43; placebo, n = 47; odds ratio, 0.73; P = .33; 95% confidence interval, 0.39-1.36). Granisetron was not effective in controlling gastroenteritis-related vomiting subsequent to discharge from ED. It did not change the expected course of the illness. Copyright © 2014 Elsevier Inc. All rights reserved.

Tolerance and dose-volume relationship of intrathoracic stomach irradiation after esophagectomy for patients with thoracic esophageal squamous cell carcinoma

PubMed Central

Fu, Xiao-Long; Chen, Jun-Chao; Xiang, Jia-Qing

2015-01-01

Purpose To identify the tolerance of radiation with a high prescribed dose and predictors for the development of intrathoracic stomach toxicity in patients with thoracic esophageal squamous cell carcinoma (SCC) after esophagectomy followed by gastric conduit reconstruction. Methods and Materials From 2011 to 2013, 105 patients after esophagectomy were treated with postoperative radiotherapy. The intrathoracic stomach was outlined with the calculation of a dose-volume histogram (DVH) for the initial intended treatment of 6020 cGy or 6300 cGy. The volume of the intrathoracic stomach receiving each dose was recorded at 10-Gy intervals between 10 and 40 Gy and at 5-Gy intervals between 40 and 60 Gy. The grade of toxicities was defined by the National Cancer Institute Common Toxicity Criteria version 4.0. Results The mean and maximum doses of the intrathoracic stomach were 2449 ± 986 cGy and 6519 ± 406 cGy, respectively. Sixteen (15.2%) and three (2.9%) experienced Common Toxicity Criteria Grade 2 and Grade 3 acute gastric toxicity. There were no Grade 4 toxicities. Fourteen patients (13.3%) exhibited late gastric complications possibly related to radiation. The volume percent of the intrathoracic stomach receiving at least 50 Gy (V50) was strongly associated with the degree of toxicity (p = 0.024, respectively). Multivariate analysis of patient and treatment-related factors revealed no other significant predictors of severe toxicities. Conclusions The intrathoracic stomach is well tolerated with a high-dose irradiation for patients with esophageal SCC receiving radiotherapy after esophagectomy. A strong dose-volume relationship exists for the development of Grade 2 acute intrathoracic stomach toxicity in our study. PMID:26314958

Hamstring Stiffness Returns More Rapidly After Static Stretching Than Range of Motion, Stretch Tolerance, and Isometric Peak Torque.

PubMed

Hatano, Genki; Suzuki, Shigeyuki; Matsuo, Shingo; Kataura, Satoshi; Yokoi, Kazuaki; Fukaya, Taizan; Fujiwara, Mitsuhiro; Asai, Yuji; Iwata, Masahiro

2017-12-18

Hamstring injuries are common, and lack of hamstring flexibility may predispose to injury. Static stretching increases range of motion (ROM) but also results in reduced muscle strength after stretching. The effects of stretching on the hamstring muscles and the duration of these effects remain unclear. To determine the effects of static stretching on the hamstrings and the duration of these effects. Randomized crossover study. University laboratory. Twenty-four healthy volunteers. We measured the torque-angle relationship (ROM, passive torque (PT) at the onset of pain, and passive stiffness) and isometric muscle force using an isokinetic dynamometer. After a 60-minute rest, the ROM of the dynamometer was set at maximum tolerable intensity; this position was maintained for 300 seconds while static passive torque (SPT) was measured continuously. We remeasured the torque-angle relationship and isometric muscle force after rest periods of 10, 20, and 30 minutes. Change in SPT during stretching; changes in ROM, PT at the onset of pain, passive stiffness, and isometric muscle force before stretching compared with 10, 20, and 30 minutes after stretching. SPT decreased significantly during stretching. Passive stiffness decreased significantly 10 and 20 minutes after stretching, but there was no significant pre- vs. post-stretching difference after 30 minutes. PT at the onset of pain and ROM increased significantly after stretching at all rest intervals, while isometric muscle force decreased significantly after all rest intervals. The effect of static stretching on passive stiffness of the hamstrings was not maintained as long as the changes in ROM, stretch tolerance, and isometric muscle force. Therefore, frequent stretching is necessary to improve the viscoelasticity of the muscle-tendon unit. Muscle force was decreased for 30 minutes after stretching; this should be considered prior to activities requiring maximal muscle strength.

Efficacy and Tolerability of Travoprost 0.004%/Timolol 0.5% Fixed-Dose Combination for the Treatment of Primary Open-Angle Glaucoma or Ocular Hypertension Inadequately Controlled with Beta-Blocker Monotherapy.

PubMed

Lerner, Simon Fabian; Park, Ki Ho; Hubatsch, Douglas A; Erichev, Valeriy; Paczka, Jose A; Roberts, Timothy V

2017-01-01

Objective . To evaluate the efficacy and tolerability of travoprost 0.004%/timolol 0.5% fixed-dose combination (TTFC) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT) inadequately controlled on beta-blocker monotherapy. Methods . In this phase IV, open-label study, 156 patients on beta-blocker monotherapy with mean intraocular pressure (IOP) between 18 and 32 mmHg were randomized (no washout period) to receive TTFC for 8 weeks (TTFC group) or to continue beta-blocker monotherapy for 4 weeks followed by TTFC for the remaining 4 weeks (beta-blocker group). Results . The mean IOP (±standard deviation) at baseline in the TTFC and beta-blocker groups was 22.5 ± 2.5 mmHg and 22.2 ± 2.3 mmHg, respectively, and at weeks 4 and 8, was 16.7 ± 3.1 mmHg and 16.1 ± 3.1 mmHg, respectively, in TTFC group and 21.1 ± 3.1 mmHg and 16.1 ± 2.8 mmHg, respectively, in the beta-blocker group. There was a significant least squares mean difference between TTFC and beta-blocker in 8 a.m. IOP at week 4 (-4.6 mmHg; one-sided 95% confidence interval [-inf, -3.9]; p < 0.0001 [primary endpoint]); the upper bound of the 95% confidence interval was within the prespecified limit (<0). Both treatments were well tolerated. Conclusion . Superior IOP control was achieved with TTFC in patients with OAG or OHT previously uncontrolled with beta-blockers. No new safety findings were identified. This trial is registered with ClinicalTrials.gov NCT02003391.

Prenatal tolerance induction: relationship between cell dose, marrow T-cells, chimerism, and tolerance.

PubMed

Chen, Jeng-Chang; Chang, Ming-Ling; Huang, Shiu-Feng; Chang, Pei-Yeh; Muench, Marcus O; Fu, Ren-Huei; Ou, Liang-Shiou; Kuo, Ming-Ling

2008-01-01

It was reported that the dose of self-antigens can determine the consequence of deletional tolerance and donor T cells are critical for tolerance induction in mixed chimeras. This study aimed at assessing the effect of cell doses and marrow T cells on engraftment and tolerance induction after prenatal bone marrow transplantation. Intraperitoneal cell transplantation was performed in FVB/N (H-2K(q)) mice at gestational day 14 with escalating doses of adult C57BL/6 (H-2K(b)) marrows. Peripheral chimerism was examined postnatally by flow cytometry and tolerance was tested by skin transplantation. Transplantation of light-density marrow cells showed a dose response. High-level chimerism emerged with a threshold dose of 5.0 x 10(6) and host leukocytes could be nearly replaced at a dose of 7.5-10.0 x 10(6). High-dose transplants conferred a steady long-lasting donor-specific tolerance but were accompanied by >50% incidence of graft-versus-host disease. Depletion of marrow T cells lessened graft-versus-host disease to the detriment of engraftment. With low-level chimerism, tolerance was a graded phenomenon dependent upon the level of chimerism. Durable chimerism within 6 months required a threshold of > or = 2% chimerism at 1 month of age and predicted a 50% chance of long-term tolerance, whereas transient chimerism (<2%) only caused hyporesponsiveness to the donor. Tolerance induction did not succeed without peripheral chimerism even if a large amount of injected donor cells persisted in the peritoneum. Neither did an increase in cell doses or donor T-cell contents benefit skin graft survivals unless it had substantially improved peripheral chimerism. Thus, peripheral chimerism level can be a simple and straightforward test to predict the degree of prenatal immune tolerance.

Fuel containment, lightning protection and damage tolerance in large composite primary aircraft structures

NASA Technical Reports Server (NTRS)

Griffin, Charles F.; James, Arthur M.

1985-01-01

The damage-tolerance characteristics of high strain-to-failure graphite fibers and toughened resins were evaluated. Test results show that conventional fuel tank sealing techniques are applicable to composite structures. Techniques were developed to prevent fuel leaks due to low-energy impact damage. For wing panels subjected to swept stroke lightning strikes, a surface protection of graphite/aluminum wire fabric and a fastener treatment proved effective in eliminating internal sparking and reducing structural damage. The technology features developed were incorporated and demonstrated in a test panel designed to meet the strength, stiffness, and damage tolerance requirements of a large commercial transport aircraft. The panel test results exceeded design requirements for all test conditions. Wing surfaces constructed with composites offer large weight savings if design allowable strains for compression can be increased from current levels.

Alternative indices of glucose homeostasis as biochemical diagnostic tests for abnormal glucose tolerance in an African setting.

PubMed

Kengne, Andre Pascal; Erasmus, Rajiv T; Levitt, Naomi S; Matsha, Tandi E

2017-04-01

Accurate diabetes diagnosis is important in Africa, where rates are increasing, and the disease largely undiagnosed. The cumbersome oral glucose tolerance test (OGTT) remains the reference standard, while alternative diagnostic methods are not yet established in Africans. We assessed the ability of fasting plasma glucose (FPG), HbA1c and fructosamine, to diagnose OGTT-based abnormal glucose tolerance in mixed-ancestry South Africans. Mixed-ancestry adults, residing in Cape Town were examined between February and November 2015. OGTT values were used to classify glucose tolerance status as: screen-detected diabetes, prediabetes, dysglycaemia (combination of diabetes and prediabetes) and normal glucose tolerance. Of the 793 participants included, 65 (8.2%) had screen-detected diabetes, 157 (19.8%) prediabetes and 571 (72.0%) normal glucose tolerance. Correlations of FPG and 2-h glucose with HbA1c (r=0.51 and 0.52) were higher than those with fructosamine (0.34 and 0.30), both p<0.0001. The highest c-statistic for the prediction of abnormal glucose tolerance was recorded with 2-h glucose [c-statistic=0.997 (screen-detected diabetes), 0.979 (prediabetes) and 0.984 (dysglycaemia)] and the lowest with fructosamine (0.865, 0.596 and 0.677). At recommended or data-specific optimal cut-offs, no combination of FPG, HbA1c and fructosamine did better than 2-h glucose, while FPG was better than HbA1c and fructosamine on a range of performance measures. Abnormal glucose tolerance in this population is overwhelmingly expressed through 2-h glucose's abnormalities; and no combination of FPG, HbA1c and fructosamine was effective at accurately discriminating OGTT-defined abnormal glucose tolerance. Tested non-glucose based strategies are unreliable alternatives to OGTT for dysglycaemia diagnosis in this population. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

SU-E-T-468: Implementation of the TG-142 QA Process for Seven Linacs with Enhanced Beam Conformance

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

Woollard, J; Ayan, A; DiCostanzo, D

2015-06-15

Purpose: To develop a TG-142 compliant QA process for 7 Varian TrueBeam linear accelerators (linacs) with enhanced beam conformance and dosimetrically matched beam models. To ensure consistent performance of all 7 linacs, the QA process should include a common set of baseline values for use in routine QA on all linacs. Methods: The TG 142 report provides recommended tests, tolerances and frequencies for quality assurance of medical accelerators. Based on the guidance provided in the report, measurement tests were developed to evaluate each of the applicable parameters listed for daily, monthly and annual QA. These tests were then performed onmore » each of our 7 new linacs as they came on line at our institution. Results: The tolerance values specified in TG-142 for each QA test are either absolute tolerances (i.e. ±2mm) or require a comparison to a baseline value. The results of our QA tests were first used to ensure that all 7 linacs were operating within the suggested tolerance values provided in TG −142 for those tests with absolute tolerances and that the performance of the linacs was adequately matched. The QA test results were then used to develop a set of common baseline values for those QA tests that require comparison to a baseline value at routine monthly and annual QA. The procedures and baseline values were incorporated into a spreadsheets for use in monthly and annual QA. Conclusion: We have developed a set of procedures for daily, monthly and annual QA of our linacs that are consistent with the TG-142 report. A common set of baseline values was developed for routine QA tests. The use of this common set of baseline values for comparison at monthly and annual QA will ensure consistent performance of all 7 linacs.« less

Alternative Confidence Interval Methods Used in the Diagnostic Accuracy Studies

PubMed Central

Gülhan, Orekıcı Temel

2016-01-01

Background/Aim. It is necessary to decide whether the newly improved methods are better than the standard or reference test or not. To decide whether the new diagnostics test is better than the gold standard test/imperfect standard test, the differences of estimated sensitivity/specificity are calculated with the help of information obtained from samples. However, to generalize this value to the population, it should be given with the confidence intervals. The aim of this study is to evaluate the confidence interval methods developed for the differences between the two dependent sensitivity/specificity values on a clinical application. Materials and Methods. In this study, confidence interval methods like Asymptotic Intervals, Conditional Intervals, Unconditional Interval, Score Intervals, and Nonparametric Methods Based on Relative Effects Intervals are used. Besides, as clinical application, data used in diagnostics study by Dickel et al. (2010) has been taken as a sample. Results. The results belonging to the alternative confidence interval methods for Nickel Sulfate, Potassium Dichromate, and Lanolin Alcohol are given as a table. Conclusion. While preferring the confidence interval methods, the researchers have to consider whether the case to be compared is single ratio or dependent binary ratio differences, the correlation coefficient between the rates in two dependent ratios and the sample sizes. PMID:27478491

Alternative Confidence Interval Methods Used in the Diagnostic Accuracy Studies.

PubMed

Erdoğan, Semra; Gülhan, Orekıcı Temel

2016-01-01

Background/Aim. It is necessary to decide whether the newly improved methods are better than the standard or reference test or not. To decide whether the new diagnostics test is better than the gold standard test/imperfect standard test, the differences of estimated sensitivity/specificity are calculated with the help of information obtained from samples. However, to generalize this value to the population, it should be given with the confidence intervals. The aim of this study is to evaluate the confidence interval methods developed for the differences between the two dependent sensitivity/specificity values on a clinical application. Materials and Methods. In this study, confidence interval methods like Asymptotic Intervals, Conditional Intervals, Unconditional Interval, Score Intervals, and Nonparametric Methods Based on Relative Effects Intervals are used. Besides, as clinical application, data used in diagnostics study by Dickel et al. (2010) has been taken as a sample. Results. The results belonging to the alternative confidence interval methods for Nickel Sulfate, Potassium Dichromate, and Lanolin Alcohol are given as a table. Conclusion. While preferring the confidence interval methods, the researchers have to consider whether the case to be compared is single ratio or dependent binary ratio differences, the correlation coefficient between the rates in two dependent ratios and the sample sizes.

Plant Distribution Data Show Broader Climatic Limits than Expert-Based Climatic Tolerance Estimates

PubMed Central

Curtis, Caroline A.; Bradley, Bethany A.

2016-01-01

Background Although increasingly sophisticated environmental measures are being applied to species distributions models, the focus remains on using climatic data to provide estimates of habitat suitability. Climatic tolerance estimates based on expert knowledge are available for a wide range of plants via the USDA PLANTS database. We aim to test how climatic tolerance inferred from plant distribution records relates to tolerance estimated by experts. Further, we use this information to identify circumstances when species distributions are more likely to approximate climatic tolerance. Methods We compiled expert knowledge estimates of minimum and maximum precipitation and minimum temperature tolerance for over 1800 conservation plant species from the ‘plant characteristics’ information in the USDA PLANTS database. We derived climatic tolerance from distribution data downloaded from the Global Biodiversity and Information Facility (GBIF) and corresponding climate from WorldClim. We compared expert-derived climatic tolerance to empirical estimates to find the difference between their inferred climate niches (ΔCN), and tested whether ΔCN was influenced by growth form or range size. Results Climate niches calculated from distribution data were significantly broader than expert-based tolerance estimates (Mann-Whitney p values << 0.001). The average plant could tolerate 24 mm lower minimum precipitation, 14 mm higher maximum precipitation, and 7° C lower minimum temperatures based on distribution data relative to expert-based tolerance estimates. Species with larger ranges had greater ΔCN for minimum precipitation and minimum temperature. For maximum precipitation and minimum temperature, forbs and grasses tended to have larger ΔCN while grasses and trees had larger ΔCN for minimum precipitation. Conclusion Our results show that distribution data are consistently broader than USDA PLANTS experts’ knowledge and likely provide more robust estimates of climatic tolerance, especially for widespread forbs and grasses. These findings suggest that widely available expert-based climatic tolerance estimates underrepresent species’ fundamental niche and likely fail to capture the realized niche. PMID:27870859

Determination of Tolerance to Internal Shorts and Its Screening in Lithium-ion Cells NASA - JSC Method

NASA Technical Reports Server (NTRS)

Jeevarajan, Judith

2009-01-01

This slide presentation reviews the method developed by the NASA Johnson Space Center (JSC) to determine tolerances to internal shorts and screening for problems in commercial off the shelf (COTS) Lithium-ion batteries. The test apparatus is shown and several examples of the usage and results of the test are discussed.

The shape of the glucose response curve during an oral glucose tolerance test heralds biomarkers of type 2 diabetes risk in obese youth

USDA-ARS?s Scientific Manuscript database

The shape of the glucose response curve during an oral glucose tolerance test (OGTT), monophasic versus biphasic, identifies physiologically distinct groups of individuals with differences in insulin secretion and sensitivity. We aimed to verify the value of the OGTT-glucose response curve against m...

Factors driving public tolerance levels and information‐seeking behaviour concerning insects in the household environment

PubMed Central

Poortvliet, P Marijn; Takken, Willem

2018-01-01

Abstract BACKGROUND The public's negative attitudes towards household insects drive tolerance for these insects and their control. Tolerance levels are important in integrated pest management (IPM), as are pest knowledge and information. The risk information seeking and processing (RISP) model describes the relationships between personal factors and information‐seeking behaviour. We combined IPM and RISP to determine important relationships between factors driving insect tolerance levels and information‐seeking behaviour through an online survey and tested whether this model is valid and generally applicable. RESULTS Relationships between variables from both IPM and RISP models were tested for seven insect species. Tolerance levels were measured with two factors: willingness to pay for pest control and whether insects are tolerated. Willingness to pay for control was positively affected by age, experience, risk perception, insect characteristics, and negative emotions and affected behavioural intention, by influencing information sufficiency and information‐seeking behaviour. Tolerability was influenced by perception of insect characteristics and determines whether control measures are taken. CONCLUSION It was possible to combine the RISP and IPM models. Relevant driving factors were a person's age, experience, risk perception, negative affective responses, tolerance levels, relevant channel beliefs about online forums, information sufficiency and information‐seeking behaviour. There was, however, variation in important factors between different insects. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:29274106

The European post-marketing observational sertindole study: an investigation of the safety of antipsychotic drug treatment.

PubMed

Kasper, Siegfried; Möller, Hans-Jürgen; Hale, Anthony

2010-02-01

The objective of the European Post-marketing Observational Serdolect((R)) (EPOS) Study was to compare the safety of treatment with Serdolect (sertindole) with that of usual treatment in patients with schizophrenia, in normal European clinical practice. The EPOS was a multicentre, multinational, referenced, cohort study. Patients were enrolled at 226 centres in ten European countries. The study was prematurely terminated in 1998 as a result of the temporary market suspension of sertindole. Termination of the study reduced the number of patients recruited from the planned 12,000 to 2,321. While the power of the study was weakened, it did provide useful mortality information, which may be useful for future long-term studies. Crude mortality in the sertindole and non-sertindole groups was 1.45 (95% confidence interval, CI 0.53-3.16) and 1.50 (CI 0.72-2.76) deaths/100 patient-years exposed, respectively. There were no more cardiac deaths in the sertindole group than in the non-sertindole group. QT interval prolongation did not translate into an increased risk of death. Sertindole was well tolerated and caused few extrapyramidal symptoms. Although CIs remained large, this post-marketing study does not provide any evidence against the use of sertindole under normal conditions. Sertindole was well tolerated and posed no significant safety problems.

In Vitro Emergence of High Persistence upon Periodic Aminoglycoside Challenge in the ESKAPE Pathogens

PubMed Central

Verstraeten, Natalie; Fauvart, Maarten

2016-01-01

Health care-associated infections present a major threat to modern medical care. Six worrisome nosocomial pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.—are collectively referred to as the “ESKAPE bugs.” They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy in vitro. We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation. In vitro cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence. PMID:27185802

Hormonal indices of tolerance to +Gz acceleration in female subjects. [personnel selection in Shuttle program

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Dallman, M. F.; Forsham, P.; Goodwin, A. L.; Leach, C. S.

1978-01-01

As a possible predictive test for screening Space Shuttle passengers, the secretions of the pituitary adrenal system and the adrenal medulla have been studied in conjunction with exposure to gravitational acceleration three times the normal level. The 12 female subjects in the test were divided into ambulatory and bedrest groups. Before bedrest, a high tolerance to centrifugation appeared to be linked to increases in plasma ACTH and cortisol. This relationship did not hold after bedrest. The correlation between tolerance to centrifugation and 24-hour urinary epinephrine-to-norepinephrine ratios was not significant.

What is your diagnosis? Marked hyperchloremia in a dog.

PubMed

Piperisova, Ida; Neel, Jennifer A; Papich, Mark G

2009-09-01

A 5-year-old neutered male Cavalier King Charles Spaniel was evaluated for a 3-week history of progressive paresis. The dog had been receiving potassium citrate capsules to acidify urine for the past 2 years because of an earlier history of urolithiasis. Results of neurologic examination, spinal cord radiography, and magnetic resonance imaging of the skull and spinal cord revealed no lesions that could have accounted for the neurologic signs. The main abnormalities on a clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference interval 108-122 mmol/L) and an anion gap of -50.4 mmol/L (reference interval 16.3-28.6 mmol/L). Because of the severe hyperchloremia, serum bromide concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which had been compounded at a local pharmacy, yielded a mean bromide concentration of 239 mg/capsule. Administration of the capsules was discontinued and there was rapid resolution of the dog's neurologic signs. This case of extreme bromide toxicity, which apparently resulted from inadvertent use of bromide instead of citrate at the pharmacy, illustrates the importance of knowing common interferents with analyte methodologies and of pursing logical additional diagnostic tests based on clinical and laboratory evidence, even when a patient's history appears to rule out a potential etiology.

[Insulin, glucagon and growth hormone responses during glucose, arginine and insulin tolerance tests in children with hyperthyroidism].

PubMed

Kato, T; Matsuura, N; Fujita, H; Fujieda, K; Nohara, Y; Mikami, Y; Abe, K; Fukushima, N

1985-06-20

There are many reports of glucose intolerance in adult patients with hyperthyroidism but few reports of glucose intolerance in hyperthyroid children. In this study, we measured plasma levels of glucose, insulin, glucagon and growth hormone in hyperthyroid children and control subjects by the use of three kinds of tolerance tests: an oral glucose tolerance test, an arginine tolerance test and an insulin tolerance test. In the oral glucose tolerance test, mean fasting glucose levels (79.6 +/- 1.4 mg/dl) rose to maximum levels (157.3 +/- 4.3 mg/dl) at 30 min in hyperthyroid children which were significantly higher than the levels in control subjects (p less than 0.01). The maximum levels of glucose fell slowly and returned to fasting levels at 180 min. In this test, plasma insulin levels increased from basal levels (12.7 +/- 1.9 microU/ml) to maximum levels (120.8 +/- 22.1 microU/ml) at 30 min in the prepubertal age group of hyperthyroidism. On the other hand, in the pubertal age group of hyperthyroidism, maximum levels of insulin were observed at 60 min, but not at 30 min. These maximum levels of insulin of both hyperthyroid age groups were significantly higher than those in the control subjects (p less than 0.05, p less than 0.01 respectively). There was no difference in insulin-glucose ratio at 30 min (delta IRI/delta BG) and insulinogenic index (I.I.) at 0 to 60 min between these two groups of hyperthyroid children and control subjects. However, I.I. at 0 to 120 min and 0 to 180 min decreased significantly in the pubertal age group of hyperthyroidism as compared with those in the control group (p less than 0.05, p less than 0.02 respectively). In the oral glucose tolerance test, plasma glucagon levels decreased from basal levels (74.1 +/- 4.3 pg/ml) to minimum levels (36.4 +/- 4.7 pg/ml) at 90 min in hyperthyroidism, which were significantly lower than those in the controls (p less than 0.05). However, there was no difference in -epsilon delta IRG/epsilon delta BG (cumulative glucagon response/cumulative glucose response) between the subjects with hyperthyroidism and the controls. On the other hand, lower responses of blood glucose, insulin, glucagon and growth hormone to arginine were observed in subjects with hyperthyroidism than in the controls. Moreover in the insulin tolerance test, there was no difference in glucagon and growth hormone response between the subjects with hyperthyroidism and the controls. Thus our conclusions are as follows: A marked increase in blood glucose after oral glucose load was observed in spite of normal insulin-glucose ratio in hyperthyroid children, suggesting the existence of peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Children's and Parents' Ability to Tolerate Child Distress: Impact on Cognitive Behavioral Therapy for Pediatric Obsessive Compulsive Disorder.

PubMed

Selles, Robert R; Franklin, Martin; Sapyta, Jeffrey; Compton, Scott N; Tommet, Doug; Jones, Richard N; Garcia, Abbe; Freeman, Jennifer

2018-04-01

The present study explored the concept of tolerance for child distress in 46 children (ages 5-8), along with their mothers and fathers, who received family-based CBT for OCD. The study sought to describe baseline tolerance, changes in tolerance with treatment, and the predictive impact of tolerance on symptom improvement. Tolerance was rated by clinicians on a single item and the CY-BOCS was used to measure OCD severity. Descriptive results suggested that all participants had some difficulty tolerating the child's distress at baseline while paired t tests indicated large improvements were made over treatment (d = 1.2-2.0). Fathers' initial tolerance was significantly related to symptom improvement in a multivariate regression as were fathers' and children's changes in distress tolerance over the course of treatment. Overall, results provide support for examining tolerance of child distress including its predictive impact and potential as a supplemental intervention target.

How do gait frequency and serum-replacement interval affect polyethylene wear in knee-wear simulator tests?

PubMed

Reinders, Jörn; Sonntag, Robert; Kretzer, Jan Philippe

2014-11-01

Polyethylene wear (PE) is known to be a limiting factor in total joint replacements. However, a standardized wear test (e.g. ISO standard) can only replicate the complex in vivo loading condition in a simplified form. In this study, two different parameters were analyzed: (a) Bovine serum, as a substitute for synovial fluid, is typically replaced every 500,000 cycles. However, a continuous regeneration takes place in vivo. How does serum-replacement interval affect the wear rate of total knee replacements? (b) Patients with an artificial joint show reduced gait frequencies compared to standardized testing. What is the influence of a reduced frequency? Three knee wear tests were run: (a) reference test (ISO), (b) testing with a shortened lubricant replacement interval, (c) testing with reduced frequency. The wear behavior was determined based on gravimetric measurements and wear particle analysis. The results showed that the reduced test frequency only had a small effect on wear behavior. Testing with 1 Hz frequency is therefore a valid method for wear testing. However, testing with a shortened replacement interval nearly doubled the wear rate. Wear particle analysis revealed only small differences in wear particle size between the different tests. Wear particles were not linearly released within one replacement interval. The ISO standard should be revised to address the marked effects of lubricant replacement interval on wear rate.

COGNITIVE FUNCTIONING AND TOLERANCE FOR DELAY OF GRATIFICATION.

ERIC Educational Resources Information Center

ZIMILES, HERBERT

TWO EXPERIMENTS WERE CONDUCTED TO STUDY THE RELATIONSHIP BETWEEN A CHILD'S TOLERANCE FOR DELAY OF GRATIFICATION AND HIS ABILITY TO CONSERVE NUMBER AND PICTURES. OTHER MEASURES OF COGNITION ALSO WERE USED. TOLERANCE FOR DELAY OF GRATIFICATION WAS MEASURED BY THE CHILD'S DECISION TO RECEIVE A PACK OF CANDY AND A TOY ON THE DAY OF TESTING OR TO…

The desert moss Pterygoneurum lamellatum (Pottiaceae) exhibits an inducible ecological strategy of desiccation tolerance: effects of rate of drying on shoot damage and regeneration

USDA-ARS?s Scientific Manuscript database

Premise of the study: Bryophytes are regarded as a clade incorporating constitutive desiccation tolerance, especially terrestrial species. Here we test the hypothesis that the opposing ecological strategy of desiccation tolerance, inducibility, is present in a desert moss, and addressed by varying r...

Melodic interval perception by normal-hearing listeners and cochlear implant users

PubMed Central

Luo, Xin; Masterson, Megan E.; Wu, Ching-Chih

2014-01-01

The perception of melodic intervals (sequential pitch differences) is essential to music perception. This study tested melodic interval perception in normal-hearing (NH) listeners and cochlear implant (CI) users. Melodic interval ranking was tested using an adaptive procedure. CI users had slightly higher interval ranking thresholds than NH listeners. Both groups' interval ranking thresholds, although not affected by root note, significantly increased with standard interval size and were higher for descending intervals than for ascending intervals. The pitch direction effect may be due to a procedural artifact or a difference in central processing. In another test, familiar melodies were played with all the intervals scaled by a single factor. Subjects rated how in tune the melodies were and adjusted the scaling factor until the melodies sounded the most in tune. CI users had lower final interval ratings and less change in interval rating as a function of scaling factor than NH listeners. For CI users, the root-mean-square error of the final scaling factors and the width of the interval rating function were significantly correlated with the average ranking threshold for ascending rather than descending intervals, suggesting that CI users may have focused on ascending intervals when rating and adjusting the melodies. PMID:25324084

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea.

PubMed

Brierley, Daniel I; Samuels, James; Duncan, Marnie; Whalley, Benjamin J; Williams, Claire M

2016-01-01

Anticipatory nausea (AN) is a poorly controlled side effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, have significant sedative effects and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. This study aims to assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Male Lister Hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-suppressed feeding (NSF) tests. CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. CBDA is very well tolerated and devoid of the sedative side effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment.

An Assessment of Fixed Interval Timing in Free-Flying Honey Bees (Apis mellifera ligustica): An Analysis of Individual Performance

PubMed Central

Craig, David Philip Arthur; Varnon, Christopher A.; Sokolowski, Michel B. C.; Wells, Harrington; Abramson, Charles I.

2014-01-01

Interval timing is a key element of foraging theory, models of predator avoidance, and competitive interactions. Although interval timing is well documented in vertebrate species, it is virtually unstudied in invertebrates. In the present experiment, we used free-flying honey bees (Apis mellifera ligustica) as a model for timing behaviors. Subjects were trained to enter a hole in an automated artificial flower to receive a nectar reinforcer (i.e. reward). Responses were continuously reinforced prior to exposure to either a fixed interval (FI) 15-sec, FI 30-sec, FI 60-sec, or FI 120-sec reinforcement schedule. We measured response rate and post-reinforcement pause within each fixed interval trial between reinforcers. Honey bees responded at higher frequencies earlier in the fixed interval suggesting subject responding did not come under traditional forms of temporal control. Response rates were lower during FI conditions compared to performance on continuous reinforcement schedules, and responding was more resistant to extinction when previously reinforced on FI schedules. However, no “scalloped” or “break-and-run” patterns of group or individual responses reinforced on FI schedules were observed; no traditional evidence of temporal control was found. Finally, longer FI schedules eventually caused all subjects to cease returning to the operant chamber indicating subjects did not tolerate the longer FI schedules. PMID:24983960

Exercise Self-Efficacy Moderates the Relation between Anxiety Sensitivity and Body Mass Index and Exercise Tolerance in Treatment-Seeking Smokers

PubMed Central

Farris, Samantha G.; Davis, Michelle L.; Rosenfield, David; Kauffman, Brooke Y.; Baird, Scarlett O.; Powers, Mark B.; Otto, Michael W.; Marcus, Bess H.; Church, Timothy S.; Smits, Jasper A. J.; Zvolensky, Michael J.

2016-01-01

There is little known about factors that contribute to the comorbidity of cigarette smoking and obesity. The current study sought to test whether exercise self-efficacy moderated the relation between anxiety sensitivity (fear of internal sensations) and BMI and exercise tolerance among cigarette smokers. Smokers (n = 72; 50% female; Mcpd = 19.3, SD = 10.65) were recruited to participate in a smoking cessation treatment trial. During medical screen, we measured weight, height, and exercise tolerance (functional capacity) employing a standardized maximal exercise testing protocol. After adjusting for participant sex and cigarettes per day, exercise self-efficacy moderated the association between anxiety sensitivity and BMI, such that the positive association between anxiety sensitivity and BMI was significantly stronger when exercise self-efficacy was low. The same pattern of results emerged for exercise tolerance. Exercise self-efficacy moderated the association between anxiety sensitivity and exercise tolerance, such that the negative association between anxiety sensitivity and exercise tolerance was significantly stronger when exercise self-efficacy was low. Among smokers, anxiety sensitivity may be a risk variable that, directly and indirectly in the context of low self-efficacy for exercise, causes or maintains higher body weight and lower exercise tolerance. PMID:27725844

Exercise Self-Efficacy Moderates the Relation between Anxiety Sensitivity and Body Mass Index and Exercise Tolerance in Treatment-Seeking Smokers.

PubMed

Farris, Samantha G; Davis, Michelle L; Rosenfield, David; Kauffman, Brooke Y; Baird, Scarlett O; Powers, Mark B; Otto, Michael W; Marcus, Bess H; Church, Timothy S; Smits, Jasper A J; Zvolensky, Michael J

2016-03-01

There is little known about factors that contribute to the comorbidity of cigarette smoking and obesity. The current study sought to test whether exercise self-efficacy moderated the relation between anxiety sensitivity (fear of internal sensations) and BMI and exercise tolerance among cigarette smokers. Smokers ( n = 72; 50% female; M cpd = 19.3, SD = 10.65) were recruited to participate in a smoking cessation treatment trial. During medical screen, we measured weight, height, and exercise tolerance (functional capacity) employing a standardized maximal exercise testing protocol. After adjusting for participant sex and cigarettes per day, exercise self-efficacy moderated the association between anxiety sensitivity and BMI, such that the positive association between anxiety sensitivity and BMI was significantly stronger when exercise self-efficacy was low. The same pattern of results emerged for exercise tolerance. Exercise self-efficacy moderated the association between anxiety sensitivity and exercise tolerance, such that the negative association between anxiety sensitivity and exercise tolerance was significantly stronger when exercise self-efficacy was low. Among smokers, anxiety sensitivity may be a risk variable that, directly and indirectly in the context of low self-efficacy for exercise, causes or maintains higher body weight and lower exercise tolerance.

Reference Intervals of Common Clinical Chemistry Analytes for Adults in Hong Kong.

PubMed

Lo, Y C; Armbruster, David A

2012-04-01

Defining reference intervals is a major challenge because of the difficulty in recruiting volunteers to participate and testing samples from a significant number of healthy reference individuals. Historical literature citation intervals are often suboptimal because they're be based on obsolete methods and/or only a small number of poorly defined reference samples. Blood donors in Hong Kong gave permission for additional blood to be collected for reference interval testing. The samples were tested for twenty-five routine analytes on the Abbott ARCHITECT clinical chemistry system. Results were analyzed using the Rhoads EP evaluator software program, which is based on the CLSI/IFCC C28-A guideline, and defines the reference interval as the 95% central range. Method specific reference intervals were established for twenty-five common clinical chemistry analytes for a Chinese ethnic population. The intervals were defined for each gender separately and for genders combined. Gender specific or combined gender intervals were adapted as appropriate for each analyte. A large number of healthy, apparently normal blood donors from a local ethnic population were tested to provide current reference intervals for a new clinical chemistry system. Intervals were determined following an accepted international guideline. Laboratories using the same or similar methodologies may adapt these intervals if deemed validated and deemed suitable for their patient population. Laboratories using different methodologies may be able to successfully adapt the intervals for their facilities using the reference interval transference technique based on a method comparison study.

Use of a New Portable Instrumented Impactor on the NASA Composite Crew Module Damage Tolerance Program

NASA Technical Reports Server (NTRS)

Jackson, Wade C.; Polis, Daniel L.

2014-01-01

Damage tolerance performance is critical to composite structures because surface impacts at relatively low energies may result in a significant strength loss. For certification, damage tolerance criteria require aerospace vehicles to meet design loads while containing damage at critical locations. Data from standard small coupon testing are difficult to apply to larger more complex structures. Due to the complexity of predicting both the impact damage and the residual properties, damage tolerance is demonstrated primarily by testing. A portable, spring-propelled, impact device was developed which allows the impact damage response to be investigated on large specimens, full-scale components, or entire vehicles. During impact, both the force history and projectile velocity are captured. The device was successfully used to demonstrate the damage tolerance performance of the NASA Composite Crew Module. The impactor was used to impact 18 different design features at impact energies up to 35 J. Detailed examples of these results are presented, showing impact force histories, damage inspection results, and response to loading.

Pharmacokinetic comparison and bioequivalence evaluation of losartan/ hydrochlorothiazide tablet between Asian Indian and Japanese volunteers.

PubMed

Kumar, Sudershan; Monif, Tausif; Khuroo, Arshad; Reyar, Simrit; Jain, Rakesh; Singla, Ajay K; Kurachi, Kazuya

2014-01-01

To demonstrate the bioequivalence between the test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablet and evaluate the effect of ethnicity on pharmacokinetics properties of losartan, losartan carboxylic acid and hydrochlorothiazide on healthy Asian Indian and Japanese volunteers. Randomized, open-label, crossover, bioavailability studies were conducted separately in healthy Asian Indian and Japanese volunteers. One tablet either of test or of reference product was administered after 10 hours of overnight fasting. After dosing, serial blood samples were collected for a period of 48 hours for both the studies. Plasma samples were analyzed for losartan, losartan carboxylic acid and hydrochlorothiazide by a validated liquid chromatographic and mass spectrometric method (LC-MS/MS). The pharmacokinetic parameters AUC0-t, AUC0-∞, Cmax, tmax, and other pharmacokinetics parameters were determined from plasma concentration-time profiles for both test and reference formulations of losartan/hydrochlorothiazide 50 + 12.5 mg tablets. Statistical evaluations were done to evaluate bioequivalence between generic test formulation (EPR0001) and Japanese reference product (Preminent®). Losartan, losartan carboxylic acid and hydrochlorothiazide were well tolerated by subjects in all periods of each study under fasted conditions. No serious adverse events were observed. The ratios of least square means for AUC0-t and Cmax and the affiliated 90% confidence intervals were within acceptance range recommended by PMDA. Marginal differences were observed in pharmacokinetic values of Asian Indian and Japanese volunteers. The results of these bioavailability studies indicate that the test formulation of losartan/hydrochlorothiazide 50 + 12.5 mg (EPR0001) tablets is bioequivalent to marketed Preminent® reference formulation in Asian Indian and Japanese volunteers, when administered under fasting conditions. Both test and reference formulations were well tolerated as a single oral dose when administered to healthy adult subjects under fasted conditions. Although Asian Indian and Japanese volunteers are ethnically different, results of these studies indicate that pharmacokinetic parameters of Asian Indian and Japanese volunteers are comparable to each other in terms of bioavailability of losartan, losartan carboxylic acid and hydrochlorothiazide. Similar least square means ratios were obtained in Asian Indian and Japanese volunteers demonstrating that a bioequivalence study conducted on Japanese volunteers seems to be substituted by Asian Indian volunteers' studies.

Depth-dependent groundwater quality sampling at City of Tallahassee test well 32, Leon County, Florida, 2013

USGS Publications Warehouse

McBride, W. Scott; Wacker, Michael A.

2015-01-01

A test well was drilled by the City of Tallahassee to assess the suitability of the site for the installation of a new well for public water supply. The test well is in Leon County in north-central Florida. The U.S. Geological Survey delineated high-permeability zones in the Upper Floridan aquifer, using borehole-geophysical data collected from the open interval of the test well. A composite water sample was collected from the open interval during high-flow conditions, and three discrete water samples were collected from specified depth intervals within the test well during low-flow conditions. Water-quality, source tracer, and age-dating results indicate that the open interval of the test well produces water of consistently high quality throughout its length. The cavernous nature of the open interval makes it likely that the highly permeable zones are interconnected in the aquifer by secondary porosity features.

Standardized likelihood ratio test for comparing several log-normal means and confidence interval for the common mean.

PubMed

Krishnamoorthy, K; Oral, Evrim

2017-12-01

Standardized likelihood ratio test (SLRT) for testing the equality of means of several log-normal distributions is proposed. The properties of the SLRT and an available modified likelihood ratio test (MLRT) and a generalized variable (GV) test are evaluated by Monte Carlo simulation and compared. Evaluation studies indicate that the SLRT is accurate even for small samples, whereas the MLRT could be quite liberal for some parameter values, and the GV test is in general conservative and less powerful than the SLRT. Furthermore, a closed-form approximate confidence interval for the common mean of several log-normal distributions is developed using the method of variance estimate recovery, and compared with the generalized confidence interval with respect to coverage probabilities and precision. Simulation studies indicate that the proposed confidence interval is accurate and better than the generalized confidence interval in terms of coverage probabilities. The methods are illustrated using two examples.

First Definition of Reference Intervals of Liver Function Tests in China: A Large-Population-Based Multi-Center Study about Healthy Adults

PubMed Central

Zhang, Chuanbao; Guo, Wei; Huang, Hengjian; Ma, Yueyun; Zhuang, Junhua; Zhang, Jie

2013-01-01

Background Reference intervals of Liver function tests are very important for the screening, diagnosis, treatment, and monitoring of liver diseases. We aim to establish common reference intervals of liver function tests specifically for the Chinese adult population. Methods A total of 3210 individuals (20–79 years) were enrolled in six representative geographical regions in China. Analytes of ALT, AST, GGT, ALP, total protein, albumin and total bilirubin were measured using three analytical systems mainly used in China. The newly established reference intervals were based on the results of traceability or multiple systems, and then validated in 21 large hospitals located nationwide qualified by the National External Quality Assessment (EQA) of China. Results We had been established reference intervals of the seven liver function tests for the Chinese adult population and found there were apparent variances of reference values for the variables for partitioning analysis such as gender(ALT, GGT, total bilirubin), age(ALP, albumin) and region(total protein). More than 86% of the 21 laboratories passed the validation in all subgroup of reference intervals and overall about 95.3% to 98.8% of the 1220 validation results fell within the range of the new reference interval for all liver function tests. In comparison with the currently recommended reference intervals in China, the single side observed proportions of out of range of reference values from our study for most of the tests deviated significantly from the nominal 2.5% such as total bilirubin (15.2%), ALP (0.2%), albumin (0.0%). Most of reference intervals in our study were obviously different from that of other races. Conclusion These used reference intervals are no longer applicable for the current Chinese population. We have established common reference intervals of liver function tests that are defined specifically for Chinese population and can be universally used among EQA-approved laboratories located all over China. PMID:24058449

Manual Physical Therapy Following Immobilization for Stable Ankle Fracture: A Case Series.

PubMed

Painter, Elizabeth E; Deyle, Gail D; Allen, Christopher; Petersen, Evan J; Croy, Theodore; Rivera, Kenneth P

2015-09-01

Case series. Ankle fractures commonly result in persistent pain, stiffness, and functional impairments. There is insufficient evidence to favor any particular rehabilitation approach after ankle fracture. The purpose of this case series was to describe an impairment-based manual physical therapy approach to treating patients with conservatively managed ankle fractures. Patients with stable ankle fractures postimmobilization were treated with manual physical therapy and exercise targeted at associated impairments in the lower limb. The primary outcome measure was the Lower Extremity Functional Scale. Secondary outcome measures included the ankle lunge test, numeric pain-rating scale, and global rating of change. Outcome measures were collected at baseline (performed within 7 days of immobilization removal) and at 4 and 12 weeks postbaseline. Eleven patients (mean age, 39.6 years; range, 18-64 years; 2 male), after ankle fracture-related immobilization (mean duration, 48 days; range, 21-75 days), were treated for an average of 6.6 sessions (range, 3-10 sessions) over a mean of 46.1 days (range, 13-81 days). Compared to baseline, statistically significant and clinically meaningful improvements were observed in Lower Extremity Functional Scale score (P = .001; mean change, 21.9 points; 95% confidence interval: 10.4, 33.4) and in the ankle lunge test (P = .001; mean change, 7.8 cm; 95% confidence interval: 3.9, 11.7) at 4 weeks. These changes persisted at 12 weeks. Statistically significant and clinically meaningful improvements in self-reported function and ankle range of motion were observed at 4 and 12 weeks following treatment with impairment-based manual physical therapy. All patients tolerated treatment well. Results suggest that this approach may have efficacy in this population. Therapy, level 4.

Impaired psychomotor function and plasma methadone and levo-alpha-acetylmethadol (LAAM) concentrations in opioid-substitution patients.

PubMed

Newcombe, David A L; Somogyi, Andrew A; Bochner, Felix; White, Jason M

2017-06-01

Tolerance to the psychomotor impairing effects of opioid drugs is expected to develop with repeated dosing, but may be incomplete. The relationship between plasma opioid concentration and psychomotor function in opioid-dependent patients was examined to determine whether impairment was more likely at the time of highest plasma drug concentration. Sixteen patients participating in a cross-over trial comparing methadone and LAAM completed a tracking task (OSPAT) 11 times over the dosing-interval for methadone (24-hrs) and LAAM (48-hrs). Venous blood was collected for the quantification of plasma (R)-(-)-methadone, LAAM, and nor-LAAM concentrations. The Digit Symbol Substitution Test (DSST) and Trail-Making Test were administered at the time of peak plasma concentration. Ten healthy controls (HCs) also participated. OSPAT scores (obtained for 15 patients) fluctuated significantly across the dosing-interval for both drugs and were lower in patients than HCs at the times of peak concentrations of (R)-(-)-methadone (1 hr: (mean difference; 95% CI) (2.13; 0.18-4.08); 2 hrs: (2.38; 0.48-4.28) postdosing) and LAAM (2 hrs: (1.81; 0.09-3.53), and 4 hrs (1.90: 0.9-3.71) postdosing). Within-participant analysis of the peak-change from baseline for OSPAT scores found that 10 of the 15 patients could be categorized as impaired on methadone and 9 on LAAM. No HCs were impaired. Patients performed worse on the DSST and Trails-A than HCs, but not on Trails-B. Results suggest that some patients receiving opioids long term may exhibit impairment at the time of highest plasma drug concentration. These patients should be made aware that their ability to undertake complex tasks may be affected. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Simulating real-life exposures to uncover possible risks to human health: A proposed consensus for a novel methodological approach.

PubMed

Tsatsakis, A M; Kouretas, D; Tzatzarakis, M N; Stivaktakis, P; Tsarouhas, K; Golokhvast, K S; Rakitskii, V N; Tutelyan, V A; Hernandez, A F; Rezaee, R; Chung, G; Fenga, C; Engin, A B; Neagu, M; Arsene, A L; Docea, A O; Gofita, E; Calina, D; Taitzoglou, I; Liesivuori, J; Hayes, A W; Gutnikov, S; Tsitsimpikou, C

2017-06-01

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.

Impact of trace metal concentrations on coccolithophore growth and morphology: laboratory simulations of Cretaceous stress

NASA Astrophysics Data System (ADS)

Faucher, Giulia; Hoffmann, Linn; Bach, Lennart T.; Bottini, Cinzia; Erba, Elisabetta; Riebesell, Ulf

2017-07-01

The Cretaceous ocean witnessed intervals of profound perturbations such as volcanic input of large amounts of CO2, anoxia, eutrophication and introduction of biologically relevant metals. Some of these extreme events were characterized by size reduction and/or morphological changes of a few calcareous nannofossil species. The correspondence between intervals of high trace metal concentrations and coccolith dwarfism suggests a negative effect of these elements on nannoplankton biocalcification processes in past oceans. In order to test this hypothesis, we explored the potential effect of a mixture of trace metals on growth and morphology of four living coccolithophore species, namely Emiliania huxleyi, Gephyrocapsa oceanica, Pleurochrysis carterae and Coccolithus pelagicus. The phylogenetic history of coccolithophores shows that the selected living species are linked to Mesozoic species showing dwarfism under excess metal concentrations. The trace metals tested were chosen to simulate the environmental stress identified in the geological record and upon known trace metal interactions with living coccolithophore algae.Our laboratory experiments demonstrated that elevated trace metal concentrations, similarly to the fossil record, affect coccolithophore algae size and/or weight. Smaller coccoliths were detected in E. huxleyi and C. pelagicus, while coccoliths of G. oceanica showed a decrease in size only at the highest trace metal concentrations. P. carterae coccolith size was unresponsive to changing trace metal concentrations. These differences among species allow discriminating the most- (P. carterae), intermediate- (E. huxleyi and G. oceanica) and least-tolerant (C. pelagicus) taxa. The fossil record and the experimental results converge on a selective response of coccolithophores to metal availability.These species-specific differences must be considered before morphological features of coccoliths are used to reconstruct paleo-chemical conditions.

Upper thermal tolerances of early life stages of freshwater mussels

USGS Publications Warehouse

Pandolfo, Tamara J.; Cope, W. Gregory; Arellano, Consuelo; Bringolf, Robert B.; Barnhart, M. Christopher; Hammer, E

2010-01-01

Freshwater mussels (order Unioniformes) fulfill an essential role in benthic aquatic communities, but also are among the most sensitive and rapidly declining faunal groups in North America. Rising water temperatures, caused by global climate change, industrial discharges, drought, or land development, could further challenge imperiled unionid communities. The aim of our study was to determine the upper thermal tolerances of the larval (glochidia) and juvenile life stages of freshwater mussels. Glochidia of 8 species of mussels were tested: Lampsilis siliquoidea, Potamilus alatus, Ligumia recta, Ellipsaria lineolata,Lasmigona complanata, Megalonaias nervosa, Alasmidonta varicosa, and Villosa delumbis. Seven of these species also were tested as juveniles. Survival trends were monitored while mussels held at 3 acclimation temperatures (17, 22, and 27°C) were exposed to a range of common and extreme water temperatures (20–42°C) in standard acute laboratory tests. The average median lethal temperature (LT50) among species in 24-h tests with glochidia was 31.6°C and ranged from 21.4 to 42.7°C. The mean LT50 in 96-h juvenile tests was 34.7°C and ranged from 32.5 to 38.8°C. Based on comparisons of LT50s, thermal tolerances differed among species for glochidia, but not for juveniles. Acclimation temperature did not affect thermal tolerance for either life stage. Our results indicate that freshwater mussels already might be living close to their upper thermal tolerances in some systems and, thus, might be at risk from rising environmental temperatures.

Impact testing of textile composite materials

NASA Technical Reports Server (NTRS)

Portanova, Marc

1995-01-01

The objectives of this report were to evaluate the impact damage resistance and damage tolerance of a variety of textile composite materials. Static indentation and impact tests were performed on the stitched and unstitched uniweave composites constructed from AS4/3501-6 Carbon/Epoxy with a fiberglass yarn woven in to hold the fibers together while being stitched. Compression and tension were measured after the tests to determine the damage resistance, residual strength and the damage tolerance of the specimens.

Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma.

PubMed

Coleman, Morton; Martin, Peter; Ruan, Jia; Furman, Richard; Niesvizky, Ruben; Elstrom, Rebecca; George, Patricia; Leonard, John; Kaufmann, Thomas

2008-03-01

The prednisone, etoposide, procarbazine and cyclophosphamide (PEP-C) oral combination chemotherapy regimen (prednisone 20 mg, cyclophosphamide 50 mg, etoposide 50 mg, and procarbazine 50 mg with an oral anti-emetic) was employed at our center to treat 22 patients with heavily pretreated, recurrent mantle cell lymphoma (MCL). All medications were administered daily until leukocytes fell to <3.0 x 10(9)/L whereupon treatment was withheld until recovery from the nadir. Therapy was then reinstituted on a daily, alternate day, or fractionated basis (e.g. 5 of 7 days) depending on patient tolerance. Doses given per day were held constant. Eighty-two percent achieved an objective response with 46% complete responses and 36% partial responses. Median time on therapy was 17 months. The regimen was well tolerated. Our findings demonstrate that low-dose oral agents administered in combination for continuous, prolonged periods with minimal drug-free intervals (metronomic therapy) may represent a novel, effective, easily tolerated approach to MCL and that this treatment approach warrants further exploration.

Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

PubMed Central

Saupe, E. E.; Hendricks, J. R.; Portell, R. W.; Dowsett, H. J.; Haywood, A.; Hunter, S. J.; Lieberman, B. S.

2014-01-01

In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species' physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species' environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species' upper and lower thermal tolerances are constrained across this interval. We find that these species' environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and future warming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species' present-day environmental requirements to future climatic landscapes to assess conservation risks. PMID:25297868

Comparing Safety and Efficacy of "Third-Generation" Antiepileptic Drugs: Long-Term Extension and Post-marketing Treatment.

PubMed

Kwok, Charlotte S; Johnson, Emily L; Krauss, Gregory L

2017-11-01

Four "third-generation" antiepileptic drugs (AEDs) were approved for adjunctive treatment of refractory focal onset seizures during the past 10 years. Long-term efficacy and safety of the drugs were demonstrated in large extension studies and in reports of subgroups of patients not studied in pivotal trials. Reviewing extension study and post-marketing outcome series for the four newer AEDs-lacosamide, perampanel, eslicarbazepine acetate and brivaracetam-can guide clinicians in treating and monitoring patients. AED extension studies evaluate treatment retention, drug tolerability, and drug safety during individualized treatment with flexible dosing and thus provide information not available in rigid pivotal trials. Patient retention in the studies ranged from 75 to 80% at 1 year and from 36 to 68% at 2-year treatment intervals. Safety findings were generally similar to those of pivotal trials, with no major safety risks identified and with several specific adverse drug effects, such as hyponatremia, reported. The third-generation AEDs, some through new mechanisms and others with improved tolerability compared to related AEDs, provide new options in efficacy and tolerability.

Macroevolutionary consequences of profound climate change on niche evolution in marine molluscs over the past three million years

USGS Publications Warehouse

Saupe, E.E.; Hendricks, J.R.; Portell, R.W.; Dowsett, Harry J.; Haywood, A. M.; Hunter, S.J.; Lieberman, B.S.

2014-01-01

In order to predict the fate of biodiversity in a rapidly changing world, we must first understand how species adapt to new environmental conditions. The long-term evolutionary dynamics of species' physiological tolerances to differing climatic regimes remain obscure. Here, we unite palaeontological and neontological data to analyse whether species' environmental tolerances remain stable across 3 Myr of profound climatic changes using 10 phylogenetically, ecologically and developmentally diverse mollusc species from the Atlantic and Gulf Coastal Plains, USA. We additionally investigate whether these species' upper and lower thermal tolerances are constrained across this interval. We find that these species' environmental preferences are stable across the duration of their lifetimes, even when faced with significant environmental perturbations. The results suggest that species will respond to current and future warming either by altering distributions to track suitable habitat or, if the pace of change is too rapid, by going extinct. Our findings also support methods that project species' present-day environmental requirements to future climatic landscapes to assess conservation risks.

Salmeterol inhaler using a non-chlorinated propellant, HFA134a: systemic pharmacodynamic activity in healthy volunteers.

PubMed Central

Kirby, S. M.; Smith, J.; Ventresca, G. P.

1995-01-01

BACKGROUND--Metered dose inhalers for the treatment of asthma use chlorofluorocarbons as propellants. These face an international ban due to their effect on the ozone layer. Salmeterol has been reformulated using the non-chlorinated propellant Glaxo inhalation grade HFA134a. METHODS--The safety, tolerability and systemic pharmacodynamic activity of the salmeterol/HFA134a inhaler, the current salmeterol inhaler, and placebo (HFA134a) were compared in 12 healthy volunteers in a double blind, randomised crossover study using a cumulative dosing design. RESULTS--Safety and tolerability were similar and the response was related to the dose over the range used (50-400 micrograms) with both salmeterol inhalers. The salmeterol/HFA134a inhaler showed no differences from the current inhaler for pulse rate, blood pressure, tremor, QTc interval, and plasma glucose levels. The salmeterol/HFA134a inhaler had significantly less effect on plasma potassium levels. CONCLUSIONS--In healthy volunteers the salmeterol/HFA134a inhaler is at least as safe and well tolerated as the current salmeterol inhaler, and has similar systemic pharmacodynamic activity. PMID:7638815

Evaluation of the Trail Making Test and interval timing as measures of cognition in healthy adults: comparisons by age, education, and gender.

PubMed

Płotek, Włodzimierz; Łyskawa, Wojciech; Kluzik, Anna; Grześkowiak, Małgorzata; Podlewski, Roland; Żaba, Zbigniew; Drobnik, Leon

2014-02-03

Human cognitive functioning can be assessed using different methods of testing. Age, level of education, and gender may influence the results of cognitive tests. The well-known Trail Making Test (TMT), which is often used to measure the frontal lobe function, and the experimental test of Interval Timing (IT) were compared. The methods used in IT included reproduction of auditory and visual stimuli, with the subsequent production of the time intervals of 1-, 2-, 5-, and 7-seconds durations with no pattern. Subjects included 64 healthy adult volunteers aged 18-63 (33 women, 31 men). Comparisons were made based on age, education, and gender. TMT was performed quickly and was influenced by age, education, and gender. All reproduced visual and produced intervals were shortened and the reproduction of auditory stimuli was more complex. Age, education, and gender have more pronounced impact on the cognitive test than on the interval timing test. The reproduction of the short auditory stimuli was more accurate in comparison to other modalities used in the IT test. The interval timing, when compared to the TMT, offers an interesting possibility of testing. Further studies are necessary to confirm the initial observation.

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

PubMed

Appleton, D J; Rand, J S; Sunvold, G D; Priest, J

2002-03-01

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation. Copyright 2002 ESFM and AAFP.

Supplementation of OmniGen-AF alters the metabolic response to a glucose tolerance test in beef heifers

USDA-ARS?s Scientific Manuscript database

This study was designed to determine whether feeding OmniGen-AF to feedlot heifers would alter metabolic profiles in response to a glucose tolerance test. Heifer calves (n=184; 216±1 kg) were allocated into 2 treatment diets: 1) Control, fed a standard receiving ration, and 2) OmniGen-AF (OG), fed t...

Impact Behavior of Composite Fan Blade Leading Edge Subcomponent with Thermoplastic Polyurethane Interleave

NASA Technical Reports Server (NTRS)

Miller, Sandi G.; Roberts, Gary D.; Kohlman, Lee W.; Heimann, Paula J.; Pereira, J. Michael; Ruggeri, Charles R.; Martin, Richard E.; McCorkle, Linda S.

2015-01-01

Impact damage tolerance and damage resistance is a critical metric for application of polymer matrix composites where failure caused by impact damage could compromise structural performance and safety. As a result, several materials and/or design approaches to improve impact damage tolerance have been investigated over the past several decades. Many composite toughening methodologies impart a trade-off between increased fracture toughness and compromised in-plane strength and modulus. In large part, mechanical tests to evaluate composite damage tolerance include static methods such as Mode I, Mode II, and mixed mode failures. However, ballistic impact damage resistance does not always correlate with static properties. The intent of this paper is to evaluate the influence of a thermoplastic polyurethane veil interleave on the static and dynamic performance of composite test articles. Static coupon tests included tension, compression, double cantilever beam, and end notch flexure. Measurement of the resistance to ballistic impact damage were made to evaluate the composites response to high speed impact. The interlayer material showed a decrease of in-plane performance with only a moderate improvement to Mode I and Mode II fracture toughness. However, significant benefit to impact damage tolerance was observed through ballistic tests.

Inhaled Mannitol as a Laryngeal and Bronchial Provocation Test.

PubMed

Tay, Tunn Ren; Hoy, Ryan; Richards, Amanda L; Paddle, Paul; Hew, Mark

2017-03-01

Timely diagnosis of vocal cord dysfunction (VCD), more recently termed "inducible laryngeal obstruction," is important because VCD is often misdiagnosed as asthma, resulting in delayed diagnosis and inappropriate treatment. Visualization of paradoxical vocal cord movement on laryngoscopy is the gold standard for diagnosis, but is limited by poor test sensitivity. Provocation tests may improve the diagnosis of VCD, but the diagnostic performance of current tests is less than ideal. Alternative provocation tests are required. This pilot study demonstrates the feasibility of using inhaled mannitol for concurrent investigation of laryngeal and bronchial hyperresponsiveness. Consecutive patients with suspected VCD seen at our institution's asthma clinic underwent flexible laryngoscopy at baseline and following mannitol challenge. VCD was diagnosed on laryngoscopy based on inspiratory adduction, or >50% expiratory adduction of the vocal cords. Bronchial hyperresponsiveness after mannitol challenge was also assessed. We evaluated the interrater agreement of postmannitol laryngoscopy between respiratory specialists and laryngologists. Fourteen patients with suspected VCD in the context of asthma evaluation were included in the study. Mannitol provocation demonstrated VCD in three of the seven patients with normal baseline laryngoscopy (42.9%). Only two patients had bronchial hyperresponsiveness. There was substantial interrater agreement between respiratory specialists and laryngologists, kappa = 0.696 (95% confidence interval: 0.324-1) (P = 0.006). Inhaled mannitol can be used to induce VCD. It is well tolerated and can evaluate laryngeal and bronchial hyperresponsiveness at the same setting. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Identification of Quantitative Trait Loci (QTL) and Candidate Genes for Cadmium Tolerance in Populus

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

Induri, Brahma R; Ellis, Danielle R; Slavov, Gancho

2012-01-01

Knowledge of genetic variation in response of Populus to heavy metals like cadmium (Cd) is an important step in understanding the underlying mechanisms of tolerance. In this study, a pseudo-backcross pedigree of Populus trichocarpa and Populus deltoides was characterized for Cd exposure. The pedigree showed significant variation for Cd tolerance thus enabling the identification of relatively tolerant and susceptible genotypes for intensive characterization. A total of 16 QTLs at logarithm of odds (LOD) ratio > 2.5, were found to be associated with total dry weight, its components, and root volume. Four major QTLs for total dry weight were mapped tomore » different linkage groups in control (LG III) and Cd conditions (LG XVI) and had opposite allelic effects on Cd tolerance, suggesting that these genomic regions were differentially controlled. The phenotypic variation explained by Cd QTL for all traits under study varied from 5.9% to 11.6% and averaged 8.2% across all QTL. Leaf Cd contents also showed significant variation suggesting the phytoextraction potential of Populus genotypes, though heritability of this trait was low (0.22). A whole-genome microarray study was conducted by using two genotypes with extreme responses for Cd tolerance in the above study and differentially expressed genes were identified. Candidate genes including CAD2 (CADMIUM SENSITIVE 2), HMA5 (HEAVY METAL ATPase5), ATGTST1 (Arabidopsis thaliana Glutathione S-Transferase1), ATGPX6 (Glutathione peroxidase 6), and ATMRP 14 (Arabidopsis thaliana Multidrug Resistance associated Protein 14) were identified from QTL intervals and microarray study. Functional characterization of these candidate genes could enhance phytoremediation capabilities of Populus.« less

Identification and Characterization of an Arabidopsis thaliana Mutant lbt With High Tolerance to Boron Deficiency

PubMed Central

Huai, Zexun; Peng, Lishun; Wang, Sheliang; Zhao, Hua; Shi, Lei; Xu, Fangsen

2018-01-01

Boron (B) is an essential micronutrient of plants. In the present study, we characterized an Arabidopsis mutant lbt with significant low-boron tolerance that was identified based on our previous mapping of QTL for B efficiency in Arabidopsis. Multiple nutrient-deficiency analyses point out that lbt mutant is insensitive to only B-limitation stress. Compared with wild-type Col-0, the fresh weight, leaf area, root length and root elongation rate of lbt mutant were significantly improved under B deficiency during vegetative growth. lbt mutant also showed the improvements in plant height, branches and inflorescences compared with Col-0 during the reproductive stage under B limitation. Ultrastructure analysis of the leaves showed that starch accumulation in lbt mutant was significantly diminished compared with Col-0. Furthermore, there were no significant differences in the expression of transporter-related genes and B concentrations between Col-0 and lbt mutant under both normal B and low-B conditions. These results suggest that lbt mutant has a lower B demand than Col-0. Genetic analysis suggests that the low-B tolerant phenotype of lbt mutant is under the control of a monogenic recessive gene. Based on the high-density SNP linkage genetic map, only one QTL for low-B tolerance was mapped on chromosome 4 between 10.4 and 14.8 Mb. No any reported B-relative genes exist in the QTL interval, suggesting that a gene with unknown function controls the tolerance of lbt to B limitation. Taken together, lbt is a low-B tolerant mutant that does not depend on the uptake or transport of B and is controlled by a monogenic recessive gene mapped on chromosome 4, and cloning and functional analysis of LBT gene are expected to reveal novel mechanisms for plant resistance to B deficiency.

On the monitoring and implications of growing damages caused by manufacturing defects in composite structures

NASA Astrophysics Data System (ADS)

Schagerl, M.; Viechtbauer, C.; Hörrmann, S.

2015-07-01

Damage tolerance is a classical safety concept for the design of aircraft structures. Basically, this approach considers possible damages in the structure, predicts the damage growth under applied loading conditions and predicts the following decrease of the structural strength. As a fundamental result the damage tolerance approach yields the maximum inspection interval, which is the time a damage grows from a detectable to a critical level. The above formulation of the damage tolerance safety concept targets on metallic structures where the damage is typically a simple fatigue crack. Fiber-reinforced polymers show a much more complex damage behavior, such as delaminationsin laminated composites. Moreover, progressive damage in composites is often initiated by manufacturing defects. The complex manufacturing processes for composite structures almost certainly yield parts with defects, e.g. pores in the matrix or undulations of fibers. From such defects growing damages may start after a certain time of operation. The demand to simplify or even avoid the inspection of composite structures has therefore led to a comeback of the traditional safe-life safety concept. The aim of the so-called safe-life flaw tolerance concept is a structure that is capable of carrying the static loads during operation, despite significant damages and after a representative fatigue load spectrum. A structure with this property does not need to be inspected, respectively monitored at all during its service life. However, its load carrying capability is thereby not fully utilized. This article presents the possible refinement of the state-of-the-art safe-life flaw tolerance concept for composite structures towards a damage tolerance approach considering also the influence of manufacturing defects on damage initiation and growth. Based on fundamental physical relations and experimental observations the challenges when developing damage growth and residual strength curves are discussed.

Multienvironment Quantitative Trait Loci Analysis for Photosynthate Acquisition, Accumulation, and Remobilization Traits in Common Bean Under Drought Stress

PubMed Central

Asfaw, Asrat; Blair, Matthew W.; Struik, Paul C.

2012-01-01

Many of the world’s common bean (Phaseolus vulgaris L.) growing regions are prone to either intermittent or terminal drought stress, making drought the primary cause of yield loss under farmers’ field conditions. Improved photosynthate acquisition, accumulation, and then remobilization have been observed as important mechanisms for adaptation to drought stress. The objective of this study was to tag quantitative trait loci (QTL) for photosynthate acquisition, accumulation, and remobilization to grain by using a recombinant inbred line population developed from the Mesoamerican intragenepool cross of drought-susceptible DOR364 and drought-tolerant BAT477 grown under eight environments differing in drought stress across two continents: Africa and South America. The recombinant inbred line population expressed quantitative variation and transgressive segregation for 11 traits associated with drought tolerance. QTL were detected by both a mixed multienvironment model and by composite interval mapping for each environment using a linkage map constructed with 165 genetic markers that covered 11 linkage groups of the common bean genome. In the multienvironment, mixed model, nine QTL were detected for 10 drought stress tolerance mechanism traits found on six of the 11 linkage groups. Significant QTL × environment interaction was observed for six of the nine QTL. QTL × environment interaction was of the cross-over type for three of the six significant QTL with contrasting effect of the parental alleles across different environments. In the composite interval mapping, we found 69 QTL in total. The majority of these were found for Palmira (47) or Awassa (18), with fewer in Malawi (4). Phenotypic variation explained by QTL in single environments ranged up to 37%, and the most consistent QTL were for Soil Plant Analysis Development (SPAD) leaf chlorophyll reading and pod partitioning traits. QTL alignment between the two detection methods showed that yield QTL on b08 and stem carbohydrate QTL on b05 were most consistent between the multilocation model and the single environment detection. Our results indicate the relevance of QTL detection in the sites in which bean breeding will be undertaken and the importance of photosynthate accumulation as a trait for common bean drought tolerance. PMID:22670228

Multienvironment quantitative trait Loci analysis for photosynthate acquisition, accumulation, and remobilization traits in common bean under drought stress.

PubMed

Asfaw, Asrat; Blair, Matthew W; Struik, Paul C

2012-05-01

Many of the world's common bean (Phaseolus vulgaris L.) growing regions are prone to either intermittent or terminal drought stress, making drought the primary cause of yield loss under farmers' field conditions. Improved photosynthate acquisition, accumulation, and then remobilization have been observed as important mechanisms for adaptation to drought stress. The objective of this study was to tag quantitative trait loci (QTL) for photosynthate acquisition, accumulation, and remobilization to grain by using a recombinant inbred line population developed from the Mesoamerican intragenepool cross of drought-susceptible DOR364 and drought-tolerant BAT477 grown under eight environments differing in drought stress across two continents: Africa and South America. The recombinant inbred line population expressed quantitative variation and transgressive segregation for 11 traits associated with drought tolerance. QTL were detected by both a mixed multienvironment model and by composite interval mapping for each environment using a linkage map constructed with 165 genetic markers that covered 11 linkage groups of the common bean genome. In the multienvironment, mixed model, nine QTL were detected for 10 drought stress tolerance mechanism traits found on six of the 11 linkage groups. Significant QTL × environment interaction was observed for six of the nine QTL. QTL × environment interaction was of the cross-over type for three of the six significant QTL with contrasting effect of the parental alleles across different environments. In the composite interval mapping, we found 69 QTL in total. The majority of these were found for Palmira (47) or Awassa (18), with fewer in Malawi (4). Phenotypic variation explained by QTL in single environments ranged up to 37%, and the most consistent QTL were for Soil Plant Analysis Development (SPAD) leaf chlorophyll reading and pod partitioning traits. QTL alignment between the two detection methods showed that yield QTL on b08 and stem carbohydrate QTL on b05 were most consistent between the multilocation model and the single environment detection. Our results indicate the relevance of QTL detection in the sites in which bean breeding will be undertaken and the importance of photosynthate accumulation as a trait for common bean drought tolerance.

Metabolic Syndrome Components After Pediatric Liver Transplantation: Prevalence and the Impact of Obesity and Immunosuppression.

PubMed

Perito, E R; Lustig, R H; Rosenthal, P

2016-06-01

Metabolic syndrome is associated with long-term morbidity and mortality after adult liver transplantation (LT). Whether pediatric LT recipients have a higher prevalence of metabolic syndrome remains controversial. In a cross-sectional study, we evaluated pediatric LT recipients aged 8-30 years using National Health and Nutrition Examination Survey (NHANES) protocols. LT recipients were matched by gender, race/ethnicity, and age with controls from NHANES. Pediatric LT recipients (n = 83), after adjusting for overweight/obesity and glucocorticoid use, had increased prevalence of prehypertension and hypertension, impaired glucose tolerance (IGT; 2-h glucose after oral glucose tolerance test ≥140 mg/dL), and low high-density lipoprotein compared to matched NHANES controls (n = 235) despite a lower prevalence of overweight/obesity. Among LT recipients, the adjusted odds of IGT doubled for every 7.5 years taking calcineurin inhibitors (odds ratio = 2.10, 95% confidence interval 1.06-4.17 per 7.5 years taking calcineurin inhibitors, p = 0.03). Among all subjects with IGT, LT recipients had a lower prevalence of overweight/obesity and less insulin resistance (homeostatic model assessment of insulin resistance) than did controls with IGT. Among normal weight subjects, LT recipients were significantly more likely than controls to have prehypertension/hypertension, IGT, low high-density lipoprotein, and metabolic syndrome. Pediatric LT recipients have unique metabolic syndrome profiles and risk factors and will require tailored screening and management protocols. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting.

PubMed

Chiocca, E Antonio; Abbed, Khalid M; Tatter, Stephen; Louis, David N; Hochberg, Fred H; Barker, Fred; Kracher, Jean; Grossman, Stuart A; Fisher, Joy D; Carson, Kathryn; Rosenblum, Mark; Mikkelsen, Tom; Olson, Jeff; Markert, James; Rosenfeld, Steven; Nabors, L Burt; Brem, Steven; Phuphanich, Surasak; Freeman, Scott; Kaplan, Rick; Zwiebel, James

2004-11-01

ONYX-015 is an oncolytic virus untested as a treatment for malignant glioma. The NABTT CNS Consortium conducted a dose-escalation trial of intracerebral injections of ONYX-015. Cohorts of six patients at each dose level received doses of vector from 10(7) plaque-forming units (pfu) to 10(10) pfu into a total of 10 sites within the resected glioma cavity. Adverse events were identified on physical exams and testing of hematologic, renal, and liver functions. Efficacy data were obtained from serial MRI scans. None of the 24 patients experienced serious adverse events related to ONYX-015. The maximum tolerated dose was not reached at 10(10) pfu. The median time to progression after treatment with ONYX-015 was 46 days (range 13 to 452 + days). The median survival time was 6.2 months (range 1.3 to 28.0 + months). One patient has not progressed and 1 patient showed regression of interval-increased enhancement. With more than 19 months of follow-up, 1/6 recipients at a dose of 10(9) and 2/6 at a dose of 10(10) pfu remain alive. In 2 patients who underwent a second resection 3 months after ONYX-015 injection, a lymphocytic and plasmacytoid cell infiltrate was observed. Injection of ONYX-015 into glioma cavities is well tolerated at doses up to 10(10) pfu.

A study of cycle control, side effects and client's satisfaction of a low dose combined contraceptive containing ethinylestradiol/drospirenone (24/4 regimen).

PubMed

Chaiyasit, Noppadol; Taneepanichskul, Surasak

2010-05-01

To study cycle control, side effects, and satisfaction of low dose 24-day combined contraceptive containing 20 microg of Ethinylestradiol and 3 mg of Drospirenone. This was an open label, non-comparative study. The healthy females from the family planning clinic at King Chulalongkorn Memorial Hospital were assigned to receive six cycles of combined oral contraceptive containing 20 microg of ethinylestradiol and 3 mg of drospirenone administered daily for 24 days followed by 4-day hormone-free interval. Data were collected on cycle control, side effects, and satisfaction. Data were analyzed using descriptive statistics for descriptive data and Paired t test for comparison. One hundred fifty four women were assigned the study medication, including one (0.64%) who did not start medication. In the second reference period, the occurrence of frequent and infrequent bleeding was low (2.1% and 4.9%). Only one woman (0.65%) discontinued medication because of irregular bleeding. There was no pregnancy reported during the present study. Overall, the study medication was well tolerated and five subjects (3.24%) discontinued study because of side effects. No serious side effects related to the study medication were reported. The majority of women (84.2%) were satisfied and very satisfied with the treatment and most (73.3%) would continue the medication if it were available. The low dose combined contraceptive containing Ethinylestradiol/Drospirenone (24/4 regimen) has acceptable cycle control and good tolerability.

Copper tolerance and copper accumulation of herbaceous plants colonizing inactive California copper mines

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

Kruckeberg, A.L.; Wu, L.

1992-06-01

Herbaceous plant species colonizing four copper mine waste sites in northern California were investigated for copper tolerance and copper accumulation. Copper tolerance was found in plant species colonizing soils with high concentrations of soil copper. Seven of the eight plant species tested were found at more than one copper mine. The mines are geographically isolated, which makes dispersal of seeds from one mine to another unlikely. Tolerance has probably evolved independently at each site. The nontolerant field control population of Vulpia microstachya displays significantly higher tolerance to copper at all copper concentration levels tested than the nontolerant Vulpia myrous population,more » and the degree of copper tolerance attained by V. microstachya at the two copper mines was much greater than that found in V. myrous. It suggests that even in these two closely related species, the innate tolerance in their nontolerant populations may reflect their potential for evolution of copper tolerance and their ability to initially colonize copper mine waste sites. The shoot tissue of the copper mine plants of Arenaria douglasii, Bromous mollis, and V. microstachya accumulated less copper than those plants of the same species from the field control sites when the two were grown in identical conditions in nutrient solution containing copper. The root tissue of these mine plants contain more copper than the roots of the nonmine plants. This result suggests that exclusion of copper from the shoots, in part by immobilization in the roots, may be a feature of copper tolerance. No difference in the tissue copper concentration was detected between tolerant and nontolerant plants of Lotus purshianus, Lupinus bicolor, and Trifolium pratense even though the root tissue had more copper than the leaves.« less

Genomic selection for tolerance to heat stress in Australian dairy cattle.

PubMed

Nguyen, Thuy T T; Bowman, Phil J; Haile-Mariam, Mekonnen; Pryce, Jennie E; Hayes, Benjamin J

2016-04-01

Temperature and humidity levels above a certain threshold decrease milk production in dairy cattle, and genetic variation is associated with the amount of lost production. To enable selection for improved heat tolerance, the aim of this study was to develop genomic estimated breeding values (GEBV) for heat tolerance in dairy cattle. Heat tolerance was defined as the rate of decline in production under heat stress. We combined herd test-day recording data from 366,835 Holstein and 76,852 Jersey cows with daily temperature and humidity measurements from weather stations closest to the tested herds for test days between 2003 and 2013. We used daily mean values of temperature-humidity index averaged for the day of test and the 4 previous days as the measure of heat stress. Tolerance to heat stress was estimated for each cow using a random regression model with a common threshold of temperature-humidity index=60 for all cows. The slope solutions for cows from this model were used to define the daughter trait deviations of their sires. Genomic best linear unbiased prediction was used to calculate GEBV for heat tolerance for milk, fat, and protein yield. Two reference populations were used, the first consisted of genotyped sires only (2,300 Holstein and 575 Jersey sires), and the other included genotyped sires and cows (2,189 Holstein and 1,188 Jersey cows). The remainder of the genotyped sires were used as a validation set. All animals had genotypes for 632,003 single nucleotide polymorphisms. When using only genotyped sires in the reference set and only the first parity data, the accuracy of GEBV for heat tolerance in relation to changes in milk, fat, and protein yield were 0.48, 0.50, and 0.49 in the Holstein validation sires and 0.44, 0.61, and 0.53 in the Jersey validation sires, respectively. Some slight improvement in the accuracy of prediction was achieved when cows were included in the reference population for Holsteins. No clear improvements in the accuracy of genomic prediction were observed when data from the second and third parities were included. Correlations of GEBV for heat tolerance with Australian Breeding Values for other traits suggested heat tolerance had a favorable genetic correlation with fertility (0.29-0.39 in Holsteins and 0.15-0.27 in Jerseys), but unfavorable correlations for some production traits. Options to improve heat tolerance with genomic selection in Australian dairy cattle are discussed. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A comparison of hydroponic and soil-based screening methods to identify salt tolerance in the field in barley

PubMed Central

Tavakkoli, Ehsan; Fatehi, Foad; Rengasamy, Pichu; McDonald, Glenn K.

2012-01-01

Success in breeding crops for yield and other quantitative traits depends on the use of methods to evaluate genotypes accurately under field conditions. Although many screening criteria have been suggested to distinguish between genotypes for their salt tolerance under controlled environmental conditions, there is a need to test these criteria in the field. In this study, the salt tolerance, ion concentrations, and accumulation of compatible solutes of genotypes of barley with a range of putative salt tolerance were investigated using three growing conditions (hydroponics, soil in pots, and natural saline field). Initially, 60 genotypes of barley were screened for their salt tolerance and uptake of Na+, Cl–, and K+ at 150 mM NaCl and, based on this, a subset of 15 genotypes was selected for testing in pots and in the field. Expression of salt tolerance in saline solution culture was not a reliable indicator of the differences in salt tolerance between barley plants that were evident in saline soil-based comparisons. Significant correlations were observed in the rankings of genotypes on the basis of their grain yield production at a moderately saline field site and their relative shoot growth in pots at ECe 7.2 [Spearman’s rank correlation (rs)=0.79] and ECe 15.3 (rs=0.82) and the crucial parameter of leaf Na+ (rs=0.72) and Cl– (rs=0.82) concentrations at ECe 7.2 dS m−1. This work has established screening procedures that correlated well with grain yield at sites with moderate levels of soil salinity. This study also showed that both salt exclusion and osmotic tolerance are involved in salt tolerance and that the relative importance of these traits may differ with the severity of the salt stress. In soil, ion exclusion tended to be more important at low to moderate levels of stress but osmotic stress became more important at higher stress levels. Salt exclusion coupled with a synthesis of organic solutes were shown to be important components of salt tolerance in the tolerant genotypes and further field tests of these plants under stress conditions will help to verify their potential utility in crop-improvement programmes. PMID:22442423

Mercury-binding proteins in the slipper limpet, Crepidula fornicata, exposed to increased soluble mercury

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

Harrison, F.L.; Watness, K.; Nelson, D.A.

1987-03-01

Crepidula fornicata were held in a flow-through bioassay system and exposed to sand-filtered seawater to which no soluble mercury (control) was added or to which either 5, 25, or 50 {mu}g l{sup {minus}1} soluble Hg was added. At specific intervals during the 16-week experiment, a group of limpets was removed from each tank; one subgroup was exposed for 48 h to high concentrations of Hg, and another was analyzed for Hg-binding proteins by gel-permeation chromatography and spectrometry. Mortality from exposure to Hg in the 48-Hg acute toxicity tests was related to concentrations of Hg experienced both during the long-term exposuremore » period and the 48-h exposure period. Chronic exposure to low levels of Hg resulted in increased amounts of total Hg in the whole body and in the low-molecular-weight Hg-binding proteins. No evidence was found for increased tolerance of Hg with preexposure.« less

A coaxial radial opening switch for a distributed-energy-store rail launcher

NASA Astrophysics Data System (ADS)

Upshaw, J. L.; Zowarka, R. C.

1984-03-01

The design, fabrication, and initial testing results for a coaxial radial opening switch for a distributed-energy-store rail launcher are presented. In this nonarcing switch, the voltage needed to transfer current to the rail launcher is generated in a fixed resistor sized to absorb the energy required to accomplish the switching. The coaxial geometry consisting of concentric rings allowed flexibility in defining the conductive and resistive portions of the switch, and also provided tight coupling by minimizing the inductance of the current path between the charging path and the load path to minimize the energy absorption requirements. The resistive portion of the switch is composed of a series of stacked circular steel ring laminations. Switching is completed in three intervals through radial actuation. The switch parts were machined from ETP 110 electrical tough pitch copper plate, 2000 series aluminum plate, and close-tolerance standed GFR epoxy. Current may be transferred at levels less than 20 kA.

Motivation as a predictor of speech intelligibility after total laryngectomy.

PubMed

Singer, Susanne; Meyer, Alexandra; Fuchs, Michael; Schock, Juliane; Pabst, Friedemann; Vogel, Hans-Joachim; Oeken, Jens; Sandner, Annett; Koscielny, Sven; Hormes, Karl; Breitenstein, Kerstin; Dietz, Andreas

2013-06-01

It has often been argued that if patients' success with speech rehabilitation after laryngectomy is limited, it is the result of lacking motivation on their part. This project investigated the role of motivation in speech rehabilitation. In a multicenter prospective cohort study, 141 laryngectomees were interviewed at the beginning of rehabilitation and 1 year after laryngectomy. Speech intelligibility was measured with a standardized test, and patients self-assessed their own motivation shortly after the surgery. Logistic regression, adjusted for several theory-based confounding factors, was used to assess the impact of motivation on speech intelligibility. Speech intelligibility 1 year after laryngectomy was not significantly associated with the level of motivation at the beginning of rehabilitation (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.7-2.3; p = .43) after adjusting for the effect of potential confounders (implantation of a voice prosthesis, patient's cognitive abilities, frustration tolerance, physical functioning, and type of rehabilitation). Motivation is not a strong predictor of speech intelligibility 1 year after laryngectomy. Copyright © 2012 Wiley Periodicals, Inc.

The peer effect on pain tolerance.

PubMed

Engebretsen, Solveig; Frigessi, Arnoldo; Engø-Monsen, Kenth; Furberg, Anne-Sofie; Stubhaug, Audun; de Blasio, Birgitte Freiesleben; Nielsen, Christopher Sivert

2018-05-19

Twin studies have found that approximately half of the variance in pain tolerance can be explained by genetic factors, while shared family environment has a negligible effect. Hence, a large proportion of the variance in pain tolerance is explained by the (non-shared) unique environment. The social environment beyond the family is a potential candidate for explaining some of the variance in pain tolerance. Numerous individual traits have previously shown to be associated with friendship ties. In this study, we investigate whether pain tolerance is associated with friendship ties. We study the friendship effect on pain tolerance by considering data from the Tromsø Study: Fit Futures I, which contains pain tolerance measurements and social network information for adolescents attending first year of upper secondary school in the Tromsø area in Northern Norway. Pain tolerance was measured with the cold-pressor test (primary outcome), contact heat and pressure algometry. We analyse the data by using statistical methods from social network analysis. Specifically, we compute pairwise correlations in pain tolerance among friends. We also fit network autocorrelation models to the data, where the pain tolerance of an individual is explained by (among other factors) the average pain tolerance of the individual's friends. We find a significant and positive relationship between the pain tolerance of an individual and the pain tolerance of their friends. The estimated effect is that for every 1 s increase in friends' average cold-pressor tolerance time, the expected cold-pressor pain tolerance of the individual increases by 0.21 s (p-value: 0.0049, sample size n=997). This estimated effect is controlled for sex. The friendship effect remains significant when controlling for potential confounders such as lifestyle factors and test sequence among the students. Further investigating the role of sex on this friendship effect, we only find a significant peer effect of male friends on males, while there is no significant effect of friends' average pain tolerance on females in stratified analyses. Similar, but somewhat lower estimates were obtained for the other pain modalities. We find a positive and significant peer effect in pain tolerance. Hence, there is a significant tendency for students to be friends with others with similar pain tolerance. Sex-stratified analyses show that the only significant effect is the effect of male friends on males. Two different processes can explain the friendship effect in pain tolerance, selection and social transmission. Individuals might select friends directly due to similarity in pain tolerance, or indirectly through similarity in other confounding variables that affect pain tolerance. Alternatively, there is an influence effect among friends either directly in pain tolerance, or indirectly through other variables that affect pain tolerance. If there is indeed a social influence effect in pain tolerance, then the social environment can account for some of the unique environmental variance in pain tolerance. If so, it is possible to therapeutically affect pain tolerance through alteration of the social environment.

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes.

PubMed

Tura, A; Mari, A; Prikoszovich, T; Pacini, G; Kautzky-Willer, A

2008-08-01

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Development of an ADC radiation tolerance characterization system for the upgrade of the ATLAS LAr calorimeter

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

Liu, Hong-Bin; Chen, Hu-Cheng; Chen, Kai

ATLAS LAr calorimeter will undergo its Phase-I upgrade during the long shutdown (LS2) in 2018, and a new LAr Trigger Digitizer Board (LTDB) will be designed and installed. Several commercial-off-the-shelf (COTS) multi-channel high-speed ADCs have been selected as possible backups of the radiation tolerant ADC ASICs for the LTDB. Here, to evaluate the radiation tolerance of these backup commercial ADCs, we developed an ADC radiation tolerance characterization system, which includes the ADC boards, data acquisition (DAQ) board, signal generator, external power supplies and a host computer. The ADC board is custom designed for different ADCs, with ADC drivers and clockmore » distribution circuits integrated on board. The Xilinx ZC706 FPGA development board is used as a DAQ board. The data from the ADC are routed to the FPGA through the FMC (FPGA Mezzanine Card) connector, de-serialized and monitored by the FPGA, and then transmitted to the host computer through the Gigabit Ethernet. A software program has been developed with Python, and all the commands are sent to the DAQ board through Gigabit Ethernet by this program. Two ADC boards have been designed for the ADC, ADS52J90 from Texas Instruments and AD9249 from Analog Devices respectively. TID tests for both ADCs have been performed at BNL, and an SEE test for the ADS52J90 has been performed at Massachusetts General Hospital (MGH). Test results have been analyzed and presented. The test results demonstrate that this test system is very versatile, and works well for the radiation tolerance characterization of commercial multi-channel high-speed ADCs for the upgrade of the ATLAS LAr calorimeter. It is applicable to other collider physics experiments where radiation tolerance is required as well.« less

Development of an ADC radiation tolerance characterization system for the upgrade of the ATLAS LAr calorimeter

DOE PAGES

Liu, Hong-Bin; Chen, Hu-Cheng; Chen, Kai; ...

2017-02-01

ATLAS LAr calorimeter will undergo its Phase-I upgrade during the long shutdown (LS2) in 2018, and a new LAr Trigger Digitizer Board (LTDB) will be designed and installed. Several commercial-off-the-shelf (COTS) multi-channel high-speed ADCs have been selected as possible backups of the radiation tolerant ADC ASICs for the LTDB. Here, to evaluate the radiation tolerance of these backup commercial ADCs, we developed an ADC radiation tolerance characterization system, which includes the ADC boards, data acquisition (DAQ) board, signal generator, external power supplies and a host computer. The ADC board is custom designed for different ADCs, with ADC drivers and clockmore » distribution circuits integrated on board. The Xilinx ZC706 FPGA development board is used as a DAQ board. The data from the ADC are routed to the FPGA through the FMC (FPGA Mezzanine Card) connector, de-serialized and monitored by the FPGA, and then transmitted to the host computer through the Gigabit Ethernet. A software program has been developed with Python, and all the commands are sent to the DAQ board through Gigabit Ethernet by this program. Two ADC boards have been designed for the ADC, ADS52J90 from Texas Instruments and AD9249 from Analog Devices respectively. TID tests for both ADCs have been performed at BNL, and an SEE test for the ADS52J90 has been performed at Massachusetts General Hospital (MGH). Test results have been analyzed and presented. The test results demonstrate that this test system is very versatile, and works well for the radiation tolerance characterization of commercial multi-channel high-speed ADCs for the upgrade of the ATLAS LAr calorimeter. It is applicable to other collider physics experiments where radiation tolerance is required as well.« less

Development of an ADC radiation tolerance characterization system for the upgrade of the ATLAS LAr calorimeter

NASA Astrophysics Data System (ADS)

Liu, Hong-Bin; Chen, Hu-Cheng; Chen, Kai; Kierstead, James; Lanni, Francesco; Takai, Helio; Jin, Ge

2017-02-01

ATLAS LAr calorimeter will undergo its Phase-I upgrade during the long shutdown (LS2) in 2018, and a new LAr Trigger Digitizer Board (LTDB) will be designed and installed. Several commercial-off-the-shelf (COTS) multi-channel high-speed ADCs have been selected as possible backups of the radiation tolerant ADC ASICs for the LTDB. To evaluate the radiation tolerance of these backup commercial ADCs, we developed an ADC radiation tolerance characterization system, which includes the ADC boards, data acquisition (DAQ) board, signal generator, external power supplies and a host computer. The ADC board is custom designed for different ADCs, with ADC drivers and clock distribution circuits integrated on board. The Xilinx ZC706 FPGA development board is used as a DAQ board. The data from the ADC are routed to the FPGA through the FMC (FPGA Mezzanine Card) connector, de-serialized and monitored by the FPGA, and then transmitted to the host computer through the Gigabit Ethernet. A software program has been developed with Python, and all the commands are sent to the DAQ board through Gigabit Ethernet by this program. Two ADC boards have been designed for the ADC, ADS52J90 from Texas Instruments and AD9249 from Analog Devices respectively. TID tests for both ADCs have been performed at BNL, and an SEE test for the ADS52J90 has been performed at Massachusetts General Hospital (MGH). Test results have been analyzed and presented. The test results demonstrate that this test system is very versatile, and works well for the radiation tolerance characterization of commercial multi-channel high-speed ADCs for the upgrade of the ATLAS LAr calorimeter. It is applicable to other collider physics experiments where radiation tolerance is required as well. Supported by the U. S. Department of Energy (DE-SC001270)

The effects of high intensity interval training in women with rheumatic disease: a pilot study.

PubMed

Sandstad, Janne; Stensvold, Dorthe; Hoff, Mari; Nes, Bjarne M; Arbo, Ingerid; Bye, Anja

2015-10-01

Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are inflammatory diseases which involve increased risk of cardiovascular disease (CVD). High intensity interval training (HIIT) is known to be effective in improving cardiovascular health. The aim of this study was to investigate whether 10 weeks of HIIT at 85-95% of HRmax would improve important risk factors of CVD in rheumatic patients, and if these patients would tolerate exercise intensities above today's recommendations. Seven women with RA and eleven with adult-JIA, 20-50 years, were recruited to this cross-over study. Participants performed HIIT, consisting of 4 × 4 min intervals at 85-95% of HRmax twice a week for 10 weeks on spinning bikes. Maximal oxygen uptake (VO2max), heart rate recovery, blood pressure, body composition, and blood variables were measured before and after the exercise and control period. Disease activity was determined and questionnaire data were collected. HIIT resulted in 12.2% increase in VO2max and 2.9% improvement in heart rate recovery (p < 0.05). BMI, body fat, and waist circumference decreased 1.2, 1.0, and 1.6%, respectively, whereas muscle mass increased 0.6% (p < 0.05). A trend toward decreased CRP was detected after HIIT (p = 0.08). No changes were detected in disease activity or pain. Despite rigorous high intensity exercise, no increase was detected in disease activity or pain, indicating that HIIT was well tolerated by these patients. Furthermore, HIIT had positive effects on several CVD risk factors. In light of this pilot study, HIIT seems like a promising non-pharmacological treatment strategy for patients with RA and adult-JIA.

78 FR 46267 - Trifluralin; Pesticide Tolerance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...), trifluralin was tested up to the limit dose (1000 mg/kg/day) and caused no systemic toxicity. Handler exposure... detection (ECD)) is available to enforce the tolerance expression. The method may be requested from: Chief...

Changes on protein expression associated with salinity tolerance in Brassica cell cultures.

PubMed

Martín, J P; Elavummoottil, O C; Moreno, M L

1993-09-01

The synthesis of proteins from salt-tolerant Brassica oleracea L. var. botrytis L. subvar. cauliflora (Gars.) DC. (cauliflower) cell cultures is modified in relation to controls in several features. There are nine newly induced polypeptides in tolerant cultures (absent in control conditions). Some of them are only present under low salt levels (85 mM NaCl). Another group seems to be representative of moderate and high salt levels (170 and 255 mM NaCl), and a third group is present in all the salt conditions tested. On the other hand, the synthesis of most of the polypeptides present in control conditions is modified in salt-tolerant cultures by increasing, decreasing or stopping their synthesis in any of the tested conditions. The relationship between these changes in Brassica and other plant systems is discussed.

Efficacy and safety of twice-daily pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg) in the treatment of adults with community-acquired pneumonia in a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae.

PubMed

Siquier, B; Sánchez-Alvarez, J; García-Mendez, E; Sabriá, M; Santos, J; Pallarés, R; Twynholm, M; Dal-Ré, R

2006-03-01

This randomized, double-blind, non-inferiority trial evaluated the efficacy and safety of pharmacokinetically enhanced amoxicillin/clavulanate 2000/125 mg twice daily versus amoxicillin/clavulanate 875/125 mg three times daily, both given orally for 7 or 10 days, in the treatment of adults with community-acquired pneumonia in Spain, a country with a high prevalence of penicillin-resistant Streptococcus pneumoniae. Following 2:1 randomization, 566 patients (intent-to-treat population) received either amoxicillin/clavulanate 2000/125 mg (n = 374) or amoxicillin/clavulanate 875/125 mg (n = 192). Among the patients who did not deviate from the protocol (clinical per-protocol population), clinical success at day 21-28 post-therapy (test of cure; primary efficacy endpoint) was 92.4% (266/288) for amoxicillin/clavulanate 2000/125 mg and 91.2% (135/148) for amoxicillin/clavulanate 875/125 mg (treatment difference, 1.1; 95% confidence interval, -4.4, 6.6). Bacteriological success at test of cure in the bacteriology per-protocol population was 90.8% (79/87) with amoxicillin/clavulanate 2000/125 mg and 86.0% (43/50) with amoxicillin/clavulanate 875/125 mg (treatment difference 4.8; 95% confidence interval, -6.6, 16.2). At test of cure, amoxicillin/clavulanate 2000/125 mg was clinically and bacteriologically effective against 7/7 penicillin-resistant Streptococcus pneumoniae (MIC > or = 2 mg/L) isolates (including three amoxicillin non-susceptible strains) and amoxicillin/clavulanate 875/125 mg against 5/5 isolates (including one amoxicillin non-susceptible strain). Both treatment regimens were well tolerated. Amoxicillin/clavulanate 2000/125 mg was at least as effective clinically and as safe as amoxicillin/clavulanate 875/125 mg in the treatment of community-acquired pneumonia in adults in a country with a high prevalence of penicillin-resistant S. pneumoniae and has a more convenient twice daily posology.

A Controlled Trial of the Efficacy of a Training Walking Program in Patients Recovering from Abdominal Aortic Aneurysm Surgery.

PubMed

Wnuk, Bartosz R; Durmała, Jacek; Ziaja, Krzysztof; Kotyla, Przemysław; Woźniewski, Marek; Błaszczak, Edward

2016-01-01

Major surgical procedures as well as general anesthesia contribute to muscle weakness and posture instability and may result in increased postoperative complications and functional disorders resulting from an elective operation. We aim to state the significance of backward walking as a form of interval march training with patients after abdominal aortic aneurysm surgery. Sixty-five patients were randomly divided into three subgroups and three various models of physiotherapy were applied. The participants were males, aged 65-75 years, with stable cardiologic status, absence of neurological disorders, and non-symptomatic aneurysm - non-ruptured, no pain complaints and no motor system impairments. The control group had only routine physiotherapy, since therapeutic groups I and II also had walking exercises, forward in group II and backward in group I. Both experimental groups were applied interval training. The patient data analyzed was as follows: hospitalization period-days; 6-min walking test-distance (m), training heart rate (1/min), mean speed (km/h), MET; spirometry test-FVC(L), FEV1(L), FEV1/FVC and PEF(L/s). The hospital stay period in all groups did not vary significantly. Statistical analysis showed that patients with backward walking had a statistically significantly lower reduction of walking distance in the corridor test when compared to the control group (p < 0.05). After the operation, a significant reduction of mean speed in the control group was noted in comparison with both the forward and backward walking groups (p < 0.05). No significant differences were noted between the experimental groups in average walking speed as well as in heart rate in all observed groups. Physical training applied to patients after major abdominal aortic aneurysm surgery influences sustaining the level of exercise tolerance to a small extent. Both backward and forward walking seem to be alternative methods when compared to classic post-surgery physiotherapy.

[The antigravity suit, chamberless type, as a means of increasing orthostatic tolerance after water immersion hypokinesis and acceleration].

PubMed

Shul'zhenko, E B; Kozlova, V G; Kurdin, K A; Iarov, A S; Plokhova, V G

1983-01-01

Orthostatic tolerance after 7-day dry immersion and head-to-feet acceleration was investigated on test subjects with and without an antigravity suit of bladderless type. With the suit on, the 20 min tilt test at 70 degrees prior to immersion induced less marked changes than without the suit. When the suit was on, cardiovascular reactions to tilt tests after immersion and acceleration improved. The maximum heart rate decreased from 135 +/- 4 to 101 +/- 5 beats/min (p less than 0.01), minimum stroke volume increased from 29 +/- 2 to 41 +/- 3 ml (p less than 0.05), and pulse pressure grew. Thus, an antigravity suit may help increase initial orthostatic tolerance and maintain it after the combined effect of simulated hypogravity and acceleration.

A damage tolerance comparison of IM7/8551 and IM8G/8553 carbon/epoxy composites

NASA Technical Reports Server (NTRS)

Lance, D. G.; Nettles, A. T.

1991-01-01

A damage tolerance study of two new toughened carbon fiber/epoxy resin systems was undertaken as a continuation of ongoing work into screening new opposites for resistance to foreign object impact. This report is intended to be a supplement to NASA TP 3029 in which four new fiber/resin systems were tested for damage tolerance. Instrumented drop weight impact testing was used to inflict damage to 16-ply quasi-isotropic specimens. Instrumented output data and cross-sectional examinations of the damage zone were utilized to quantify the damage. It was found that the two fiber/resin systems tested in this study were much more impact resistant than an untoughened composite such as T300/934, but were not as impact resistant as other materials previously studied.

A Lift-Off-Tolerant Magnetic Flux Leakage Testing Method for Drill Pipes at Wellhead.

PubMed

Wu, Jianbo; Fang, Hui; Li, Long; Wang, Jie; Huang, Xiaoming; Kang, Yihua; Sun, Yanhua; Tang, Chaoqing

2017-01-21

To meet the great needs for MFL (magnetic flux leakage) inspection of drill pipes at wellheads, a lift-off-tolerant MFL testing method is proposed and investigated in this paper. Firstly, a Helmholtz coil magnetization method and the whole MFL testing scheme are proposed. Then, based on the magnetic field focusing effect of ferrite cores, a lift-off-tolerant MFL sensor is developed and tested. It shows high sensitivity at a lift-off distance of 5.0 mm. Further, the follow-up high repeatability MFL probing system is designed and manufactured, which was embedded with the developed sensors. It can track the swing movement of drill pipes and allow the pipe ends to pass smoothly. Finally, the developed system is employed in a drilling field for drill pipe inspection. Test results show that the proposed method can fulfill the requirements for drill pipe inspection at wellheads, which is of great importance in drill pipe safety.

A Lift-Off-Tolerant Magnetic Flux Leakage Testing Method for Drill Pipes at Wellhead

PubMed Central

Wu, Jianbo; Fang, Hui; Li, Long; Wang, Jie; Huang, Xiaoming; Kang, Yihua; Sun, Yanhua; Tang, Chaoqing

2017-01-01

To meet the great needs for MFL (magnetic flux leakage) inspection of drill pipes at wellheads, a lift-off-tolerant MFL testing method is proposed and investigated in this paper. Firstly, a Helmholtz coil magnetization method and the whole MFL testing scheme are proposed. Then, based on the magnetic field focusing effect of ferrite cores, a lift-off-tolerant MFL sensor is developed and tested. It shows high sensitivity at a lift-off distance of 5.0 mm. Further, the follow-up high repeatability MFL probing system is designed and manufactured, which was embedded with the developed sensors. It can track the swing movement of drill pipes and allow the pipe ends to pass smoothly. Finally, the developed system is employed in a drilling field for drill pipe inspection. Test results show that the proposed method can fulfill the requirements for drill pipe inspection at wellheads, which is of great importance in drill pipe safety. PMID:28117721

[Secondary Full Title: Effects of high intensity interval training in plain and uphill regarding physical performance].

PubMed

Marterer, Natalie; Menz, Verena; Burtscher, Martin

2018-06-01

 As the number of HIITs is increasing in competitive and non-competitive sports, the risk of injuries and overload is increasing. There are no scientific data to support specific recommendations in regard to intensity, duration, number of intervals and gradient for HIIT that result in improved muscular parameters in athletes. Therefore the aim of this study was to compare HIIT in plain and uphill exercise, with respect to exercise tolerance and improvements in performance (VO 2max and 800 m running time in the plain and uphill).  17 well-trained sport students (10 females, 7 males; Ø VO 2max : 53.7 ml/min/kg) were randomly assigned to the plain group (plain; GE) (n = 8) or the uphill group (hill, GB) (n = 9). In the four weeks of training, all subjects completed 14 HIIT sessions. Each session consisted of 8 × 2 min running at 90 - 95 % of the maximal heart rate (HR max ), separated by 2 min recovery periods (work/rest ratio: 1:1). Before the intervention phase, subjects performed treadmill spirometry, a 800 m field test in the plain, as well as an 800 m uphill field test to determine baseline performance. One week after the intervention period, all subjects completed a retest of all measurements and tests. After the intervention, all subjects completed a questionnaire by giving their level of perceived exertion during training, using the BORG scale.  In GE, three subjects dropped out of the study because of overtraining. In GB, two subjects did not complete the study because of time constraints. The evaluation of the perceived exertion of the training in flat terrain showed a trend (p = 0.08; t = - 1.96) towards being perceived as more exhausting then in hilly terrain. A four week HIIT showed significant improvements in VO 2max by 5.2 % (p = 0.02; t = - 2.76), and a reduction in the running time in the plain by 4.6 % (p = 0.01; t = 3.48) and uphill by 6.3 % (p = 0.02; t = 2.77). No significant group effect was detected.  In this study, the application of HIIT leads to significant improvements in the performance of well-trained athletes. There is no evidence that the mode of training influenced the running improvements. However, uphill training tends to be better tolerated by the athletes. © Georg Thieme Verlag KG Stuttgart · New York.